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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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IGF2 expression was high in drug-resistant GIST cell lines, suggesting that IGF2 overexpression may be closely related to drug resistance.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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High expression of insulin-like growth factor 2 in gastrointestinal stromal tumors with liver metastasis and closely related to drug resistance.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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A: Differentially expressed genes in gastrointestinal stromal tumors (GIST) with liver metastasis tissues and normal gastric tissues (|log2FC| > 1; P < 0.05); B: Differentially expressed genes in imatinib sensitive and in seven Imatinib-resistant GIST patients (|log2FC| > 1; P < 0.05); C: Western blot assay of insulin-like growth factor 2 (IGF2) protein expression in GIST cell lines (GIST882, GIST882-R, GIST-T1, GIST-T1-R); D: ELISA of IGF2 expression in GIST cell lines (GIST882, GIST882-R, GIST-T1, GIST-T1-R).
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Data are mean ± standard deviation.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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P < 0.05; P < 0.01; P < 0.001.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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We transfected GIST882 and GIST-T1 cells with an IGF2 overexpressing plasmid (OE-IGF2) or a shRNA to knock down IGF2 (sh-IGF2).
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Western blotting detected the efficiency of cell transfection (Figure 2A).
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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IGF2 was highly expressed in OE-IGF2-transfected cells compared with OE-NC cells, while IGF2 expression was low in sh-IGF2-transfected cells (P < 0.001).
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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ELISA also found that IGF2 expression high in OE-IGF2 group compared with OE-NC-GIST882 and GIST-T1 cells and IGF2 was low expressed in sh-IGF2-transfected cells (Figure 2B, P < 0.05, P < 0.01, P < 0.001).
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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The CCK-8 results showed that cell viability was significantly increased after exogenous expression of IGF2, sh-IGF2 transfection inhibited GIST882 and GIST-T1 cell viability (Figure 2C, P < 0.001).
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Likewise, the Transwell assays found more migrating and invading OE-IGF2-GIST882 and GIST-T1 cells compared with their respective control cells (Figure 2D and E, P < 0.001).
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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We also found that sh-IGF2 transfection inhibited cell viability, migration and invasion.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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In addition, western blotting detect EMT-related proteins (E-cadherin, vimentin, Twist1, and N-cadherin) expression in cells.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Silencing IGF2 increased E-cadherin expression, and inhibited vimentin, Twist1, and N-cadherin expression, but IGF2 overexpression had the opposite experimental findings (Figure 2F, P < 0.001).
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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To further verify the functional role of IGF2 on the growth of GISTs, we performed nude mouse tumorigenesis experiments.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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OE-IGF2 transfected-GIST-T1 cell lines were injected into the spleen.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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We found that OE-IGF2 promoted the GIST-T1 cell metastasis in vivo, showing a significant decline in the number of liver metastatic nodules (Figure 2G and H, P < 0.01).
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Insulin-like growth factor 2 promotes malignant characteristics and metastasis of gastrointestinal stromal tumors.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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A: Western blot measured the transfection efficiency of OE-insulin-like growth factor 2 (IGF2) or sh-IGF2 in gastrointestinal stromal tumors (GIST) 882 and GIST-T1 cells; B: ELISA of IGF2 expression in OE-IGF2 or sh-IGF2 transfected GIST882 and GIST-T1 cells; C: Cell counting kit-8 assay assessed cell viability in GIST882 and GIST-T1 cells; D: Transwell assay evaluated the migration of OE-IGF2- or sh-IGF2-transfected cells (scar bar = 50 μm); E: Transwell assays of the invasiveness of OE-IGF2 or sh-IGF2 transfected cells. (
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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scar bar = 50 μm); F: Detection of proteins involved in epithelial-mesenchymal transition (vimentin, N-cadherin, E-cadherin, Twist1) in OE-IGF2 or sh-IGF2 transfected cells; G: Liver tissue from tumor xenografts in nude mice injected withOE-IGF2 transfected GIST-T1 cells; H: Liver metastasis determined by hematoxylin-eosin staining.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Data are mean ± standard deviation.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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P < 0.05; P < 0.01; P < 0.001.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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IGF1R mRNA expression was increased in GIST-T1 and GIST882 cells transfected with OE-IGF2, and IGF1R mRNA expression was decreased after sh-IGF2 transfection (Figure 3A, P < 0.001).
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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PI3K-Akt signaling is the IGF2-IGF1R signal principal downstream target.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Expression of IGF2-IGF1R pathway-associated proteins (IGF1R, p-IGF1R, PI3K, AKT, p-AKT) in GIST-T1 cells was measured by western blotting.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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IGF2 overexpression increased the expression of IGF1R, p-IGF1R, PI3K, AKT, and p-AKT in GIST-T1 cells.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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The opposite result was noted after IGF2 knockdown (Figure 3B, P < 0.01, P < 0.001).
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Although sh-IGF2 reduced IGF1R, p-IGF1R, PI3K, AKT, and p-AKT expression in GIST-T1 cells, it was partially restored by overexpression of IGF2R (Figure 3C, P < 0.01, P < 0.001).
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Insulin-like growth factor 2 activated the IGF1R signaling in gastrointestinal stromal tumors cells.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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A: Quantitative reverse transcriptase PCR assay of IGF1R mRNA expression in gastrointestinal stromal tumors (GIST) 882 and GIST-T1 cells after OE-insulin-like growth factor 2 (IGF2) or sh-IGF2 transfection; B: Detection of protein levels (IGF1R, p-IGF1R, PI3K, AKT, and p-AKT) involved in the PI3K/AKT in OE-IGF2 or sh-IGF2 transfected-GIST-T1 cells by western blot assay; C: Detection of protein levels (IGF1R, p-IGF1R, PI3K, AKT, and p-AKT) involved in the PI3K/AKT in GIST-T1 cells after sh-IGF2 and OE-IGF2R transfection by western blot assay.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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P < 0.01; P < 0.001.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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We analyzed glucose consumption and lactate production in GIST cells.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Sh-IGF2 inhibited glucose consumption (Figure 4A), and lactate production in GIST882 and GIST-T1 cells (Figure 4B), but IGF2 overexpression had the opposite experimental findings (P < 0.001).
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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To examine the role of the Warburg effect in liver metastasis of GISTs, we treated OE-NC-GIST882 and OE-IGF2-GIST882 cells with 2-deoxyglucose (2-DG, a glycolysis inhibitor) for 24 hat 0, 4, 8, and 16 mmol/L. 2-DG significantly inhibited glycolysis (Figure 4C, P < 0.05, P < 0.01, P < 0.001) and Transwell assays found that 2-DG treatment inhibited the promoting effect of OE-IGF2 on GIST882 and GIST-T1 cell invasion and migration (Figure 4D and E, P < 0.001).
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Similarly, OE-IGF2 increased vimentin, Twist1, and N-cadherin expression and inhibited E-cadherin expression in cells, but the expression was partially restored by 2-DG treatment (Figure 4F, P < 0.001).
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Insulin-like growth factor 2/IGF1R-mediatedglycolysisis required for gastrointestinal stromal tumors with liver metastasis.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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A: Extracellular acidification rate was measured; B: Lactate production in gastrointestinal stromal tumors (GIST) 882 and GIST-T1 cells transfected with sh-insulin-like growth factor 2 (IGF2) or OE-IGF2 were measured; C: Lactate production in OE-IGF2-GIST882 and GIST-T1 cells cotreated with 2-deoxy-D-glucose (2-DG) (0, 4, 8, and 16 mmol/L); D: Transwell assay of the migration ability of the OE-IGF2-cells cotreated with 2-DG (scar bar = 50 μm); E: Transwell assay of the invasiveness of OE-IGF2-cells cotreated with 2-DG (scar bar = 50 μm); F: Assay of proteins involved in epithelial-mesenchymal transition (vimentin, N-cadherin, E-cadherin, Twist1) in OE-IGF2-cells cotreated with 2-DG.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
|
Data are mean ± standard deviation.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
|
P < 0.05; P < 0.01; P < 0.001.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Figure 1 shows that IGF2 was involved in regulating drug resistance.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Next, we will further verify.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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To test whether IGF2 also regulated drug resistance in GISTs in vivo, we established a xenograft model by inoculating sh-NC or sh-IGF2-GIST-T1 cells into nude mice.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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In the sh-IGF2-GIST-T1 mouse xenograft model, tumor volume and growth were inhibited by sh-IGF2, and imatinib had the same influence on tumor growth and volume.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Combined treatment with imatinib and sh-IGF2 was more effective for reducing tumor progression than single treatment (Figure 5A-C, P < 0.001).
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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The western blot results revealed that expression of IGF1R, p-IGF1R, AKT, PI3K, and p-AKT in tumor tissue was suppressed in both sh-IGF2-transfected cells and after imatinib treatment.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Moreover, combined imatinib and sh-IGF2 were more effective than single therapy (Figure 5D, P < 0.001).
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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The above data suggest that IGF2/IGF1R regulate imatinib resistance.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Insulin-like growth factor 2/IGF1R regulates imatinib resistance of gastrointestinal stromal tumors by regulating glycolysis.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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A: Tumor growth in xenografted nude mice; B: Tumor volumes in sh-insulin-like growth factor 2 (IGF2)-gastrointestinal stromal tumors (GIST)-T1 mouse xenograft models treated with imatinib; C: After 35 d, the mice were killed and the tumors were weighed; D: Assay of IGF1R, p-IGF1R, PI3K, AKT, and p-AKT in tumor tissue by western blotting; E: Assay of drug sensitivity in OE-IGF2-GIST882 and GIST-T1 cells treated with 2-deoxy-D-glucose (2-DG); F: Flow cytometry assay of apoptosis of OE-IGF2-GIST882 and GIST-T1 cells treated with 2-DG.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
|
Data are mean ± standard deviation.
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PMC11334037
|
Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
|
P < 0.05; P < 0.01; P < 0.001.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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In addition, previous data shows that IGF2 regulates glycolysis in GIST cells.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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IGF2 regulates cell sensitivity to imatinib through its influence on glycolysis.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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We used 2-DG to inhibit glycolysis in GIST cells.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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OE-IGF2 increased drug sensitivity in GIST882 and GIST-T1 cells, but after treatment with 2-DG, transfection with OE-IGF2 no longer changed drug sensitivity in GIST cells (Figure 5E, P < 0.001).
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Flow cytometric analysis showed that sh-IGF2 suppressed imatinib-induced apoptosis and OE-IGF2 reduced imatinib-induced apoptosis in GIST cells.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Treatment with 2-DG and transfection with OE-IGF2 no longer influenced imatinib-induced apoptosis in GIST cells (Figure 5F, P < 0.001).
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Therefore, the results show that IGF2 regulated imatinib sensitivity in GIST cells by affecting glycolysis.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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GISTs is the most frequent malignant gastrointestinal sarcoma and causes significant patient harm.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Recently, anticancer drug resistance has become a significant challenge to the treatment of GISTs.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Treatment with tyrosine kinase inhibitors (TKIs) has led to substantial improvement of survival, both for patients with localized GISTs and those with advanced disease.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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As the first-line TKI, imatinib offers treatment for advanced and metastatic GISTs, adjuvant therapy in high-risk GISTs and neoadjuvant treatment to downsize large tumors prior to resection.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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We explored the mechanism of IGF2 in imatinib resistance in GISTs and whether IGF2 enhanced metastasis and imatinib resistance by driving glycolysis by targeting IGF1R signaling transduction.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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IGF2, identified as an imprinted gene, exhibits a significant impact on cancer progression when its imprinting is lost or relaxed, leading to heightened autocrine IGF2 levels and increased secretion in malignant cells.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Numerous studies have revealed the upregulation of IGF2 in various cancers such as hepatocellular carcinoma, correlating with resistance to chemotherapy and a poorer prognosis[12-14].
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Our investigation, which focused on DEGs associated with liver metastasis and drug resistance in GISTs, we observed elevated levels of IGF2 in GISTs cases linked to liver metastasis and drug resistance.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Our comprehensive analysis included assessment of cell proliferation, viability, migration, and invasiveness.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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The findings strongly suggest that overexpression of IGF2 induce the proliferation, metastasis, and EMT of GIST cells.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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IGF1R, is a tyrosine kinase receptor that can be triggered by IGF2 and has a pivotal role in regulating mammalian development, metabolism, and growth.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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IGF1R is known to be upregulated in various human solid tumors.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Its involvement in cell promoting cell proliferation and inhibiting programmed cell death is facilitated by activation of its tyrosine kinase and the subsequent engagement of the Ras/Raf/MEK and PI3K/AKT/mTOR signaling pathways.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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The IGF2-IGF1R signaling axis assumes critical significance in governing cell proliferation, differentiation, EMT, migration, drug resistance, and maintaining stemness in malignancies.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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This investigation further demonstrated the activation of IGF1R signaling by IGF2 in GIST cells.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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It highlights the role of IGF2 as a pivotal chromatin factor that controls the expression level of IGF1R and modulates downstream signaling by the PI3K/AKT pathway.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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IGF2 also upregulated the expression of glycolytic and mitochondrial respiration markers.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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IGF2 overexpression has also been shown to cause metabolic reprogramming in breast cancer.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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As expected, we also that IGF2 mediated the glycolysis in GISTs by targeting IGF1R signaling.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Increased expression of IGF2 is a common occurrence in various cancers and has been associated with increased resistance to chemotherapy, leading to a poorer prognosis.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Regarding GISTs, the standard first-line therapeutic approach involves the use of imatinib.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Imatinib, a potent TKI, is the primary treatment for GISTs, and significantly contributes to the progression-free survival of GIST patients.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Our investigation revealed a noteworthy correlation of increased IGF2 expression with the induction of GISTs resistance to imatinib concurrently with a reduction of imatinib-induced apoptosis in GIST cells.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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These findings underscore IGF2 as a potential regulator of GISTs imatinib resistance, and a promising target for interventions aimed at reversing such resistance.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Intriguingly, our study further showed that IGF2 regulates cellular sensitivity to imatinib by modulating glycolysis.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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The study had some limitations of this study.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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First, except for GIST cells, the role of IGF2 on GIST patient samples needs verification.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Even though we found that IGF-2 overexpression increased the resistance of GIST cells to imatinib in cell culture, the clinical effect needs to be verified.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Secondly, our results allows speculation that IGF2 was involved in the resistance to chemotherapy and a worse GISTs prognosis.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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However, the molecular mechanism of IGF2 specific to GISTs requires further investigation.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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We will consider these issues in future studies.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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In addition, studies have found that hypoglycemia in patients with non-islet cell tumor-induced GISTs may be aggravated by imatinib.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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A recent case study reported that a GISTs that produced big-IGF2 also caused severe hypoglycemia.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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We also hope to investigate that in future experiments.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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This study investigated IGF2 regulation of metastasis and imatinib resistance in GISTs.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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IGF2 interacted with IGF1R to regulate glycolysis.
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PMC11334037
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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.
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Our results found that IGF2 targeting of IGF1R signaling improved metastasis and imatinib chemosensitivity via driving glycolysis in GISTs and support potential use of IGF2 to reverse imatinib resistance in GISTs patients.
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PMC12101583
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Inhibitory effect of Endostar on HIF-1 with upregulation of MHC-I in lung cancer cells.
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Endostar is a human recombinant endostatin which is an attractive anti-angiogenesis protein.
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PMC12101583
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Inhibitory effect of Endostar on HIF-1 with upregulation of MHC-I in lung cancer cells.
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Because inefficient antigen presenting MHC class I expression (which can be downregulated by HIF-1) is an important strategy for cancer immune evasion, besides its anti-angiogenesis effect, it remains unclear whether Endostar has an inhibitory effect on HIF-1 expression by upregulating MHC class I expression in cancer cells to facilitate immunotherapies, including PD-1/PD-L1 inhibitors.
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PMC12101583
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Inhibitory effect of Endostar on HIF-1 with upregulation of MHC-I in lung cancer cells.
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In this study, A549 and NCI-H1299 lung cancer cells were treated with Endostar (6.25 μg/ml, 12.5 μg/ml, and 25 μg/ml, respectively).
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PMC12101583
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Inhibitory effect of Endostar on HIF-1 with upregulation of MHC-I in lung cancer cells.
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HIF-1 expression was detected by Immunocytochemistry and Western blot.
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PMC12101583
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Inhibitory effect of Endostar on HIF-1 with upregulation of MHC-I in lung cancer cells.
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Proteins of the MHC class I α-heavy chain and β2 m light chain, STAT3 and pSTAT3 were detected by Western blot.
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