Formation of the IGF1R/CAV1/SRC tri‐complex antagonizes TRAIL‐induced apoptosis in gastric cancer cells

Guo, Tianshu; Xu, Ling; Che, Xiaofang; Zhang, Simeng; Li, Ce; Wang, Jin; Gong, Jing; Ma, Rui; Fan, Yibo; Hou, Kezuo; Zhou, Hui‐Ming; Hu, Xuejun; Liu, Yunpeng; Qu, Xiujuan

doi:10.1002/cbin.10775

Cited by 11 publications

(8 citation statements)

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“…The inhibition of IR/IGF1R reduced the epithelial-mesenchymal transition and cancer stem cell-like traits in 'resistant cells' of cholangiocarcinoma [32]. The elevated expression of IGF1R was observed in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistant gastric cancer cells, thus enhancing TRAIL resistance in gastric cancer cells [33]. According to genes encoding proteins related to insulin receptors, IGF1R is able to stimulate renal cancer cells [34].…”

Section: Discussionmentioning

confidence: 99%

Identification of prognostic factors for intrahepatic cholangiocarcinoma using long non-coding RNAs-associated ceRNA network

et al. 2020

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Background: Accumulating amount of evidence has highlighted the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in tumor pathogenesis. However, the roles of long non coding RNAs (lncRNAs) in the lncRNA-related ceRNA network of intrahepatic cholangiocarcinoma (ICC) still remain enigmatic. The current study aims to identify prognostic factors in the lncRNA-related ceRNA network of ICC. Methods: The transcriptome sequencing data of lncRNAs, messenger RNA (mRNA) and microRNA (miR) were downloaded from the SRA and TCGA databases. Differentially expressed lncRNAs (DElncRNAs), DEmiRs and DEmRNAs were identified and adopted to construct an lncRNA-miR-mRNA ceRNA network. ICC-associated DEmRNAs were adopted to construct the protein-protein interaction (PPI) network. The expression of the top 6 genes in the hub module was validated with mRNA transcriptome sequencing data and ICC-related gene expression dataset GSE45001, followed by GO and KEGG pathway enrichment analysis. The relationship between the hub gene-associated ceRNA network and the overall survival of patients with ICC was predicted by conducting a Kaplan-Meier survival analysis. Results: Sixty co-expressed DEmRNAs were identified in the ceRNA network. The top 6 hub genes consisted of downregulated FOS, IGF2, FOXO1 and NTF3, upregulated IGF1R, and insignificantly downregulated HGF in ICC tissues, when compared to that of normal adjacent tissues, followed by the successful construction of lncRNA-miR-hub network consisting of 86 ceRNA modules. MME-AS1 and hsa-miR-182 were associated with overall survival in ICC patients. FOS, IGF1R, IGF2, FOXO1, and NTF3 might target "TGF-β signaling pathway", "the hedgehog signaling pathway", "retinol metabolism", or "type II diabetes mellitus" pathways respectively. Conclusion: These results indicate that FOS, IGF1R, IGF2, FOXO1, and NTF3 were useful prognostic factors in determining the prognosis of patients with ICC.

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Section: Discussionmentioning

confidence: 99%

Identification of prognostic factors for intrahepatic cholangiocarcinoma using long non-coding RNAs-associated ceRNA network

et al. 2020

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“…BGC823 and SGC7901 cells were exposed to 10, 20, and 50 μg/mL β‐elemene for 24 h. β‐elemene inhibited cell proliferation in dose‐dependent manner (Figure A). To detect if β‐elemene enhanced the sensitivity of gastric cancer cells to TRAIL, the two cells were simultaneously treated with β‐elemene (20 μg/mL) and/or TRAIL (100 ng/mL) as per our previous study (Guo et al, ). β‐elemene combined with TRAIL obviously inhibited cell viability compared to β‐elemene or TRAIL alone ( P < 0.05, Figure B).…”

Section: Resultsmentioning

confidence: 99%

β‐elemene increases the sensitivity of gastric cancer cells to TRAIL by promoting the formation of DISC in lipid rafts

Guo

et al. 2018

Cell Biology International

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β-Elemene, an anti-cancer drug extracted from traditional Chinese medicinal herb, showed anti-tumor effects on gastric cancer cells. Our previous studies reported gastric cancer cells are insensitive to TRAIL. However, whether β-elemene could enhance anti-cancer effects of TRAIL on gastric cancer cells is unknown. In our present study, β-elemene prevented gastric cancer cell viability in dose-dependent manner, and when combined with TRAIL, obviously inhibited proliferation and promoted apoptosis in gastric cancer cells. Compared to β-elemene or TRAIL alone, treatment with β-elemene and TRAIL obviously promoted DR5 clustering as well as translocation of Caspase-8, DR5 and FADD into lipid rafts. This led to cleavage of Caspase-8 and the formation of death-inducing signaling complex (DISC) in lipid rafts. The cholesterol-sequestering agent nystatin partially reversed DR5 clustering and DISC formation, preventing apoptosis triggered by the combination of β-elemene and TRAIL. Our results suggest that β-elemene increases the sensitivity of gastric cancer cells to TRAIL partially by promoting the formation of DISC in lipid rafts.

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“…The inhibition of IR/IGF1R reduced epithelial-mesenchymal transition and cancer stem cell-like traits in resistant cells of cholangiocarcinoma [26]. The elevated expression of IGF1R was observed in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistant gastric cancer cells, enhancing TRAIL resistance in gastric cancer cells [27]. As genes encoding proteins related to insulin receptor, IGF1R could stimulate renal cancer cells [28].…”

Section: Discussionmentioning

confidence: 99%

Identification of prognostic factors for intrahepatic cholangiocarcinoma based on long non-coding RNAs-associated ceRNA network

Kang

Guo

Zhu

et al. 2020

Preprint

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Background Accumulating evidence has highlighted the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in tumor biology. However, the roles of cancer long non coding RNAs (lncRNAs) in lncRNA-related ceRNA network of intrahepatic cholangiocarcinoma (ICC) remain enigmatic. The current study aims to identify prognostic factors in the lncRNA-related ceRNA network of ICC. Methods The transcriptome sequencing data of the lncRNAs, messenger RNA (mRNA) and microRNA (miR) were downloaded from SRA, and TCGA database respectively. Differentially expressed lncRNAs (DElncRNAs), DEmiRs and DEmRNAs were identified and adopted to construct lncRNA-miR-mRNA ceRNA network. ICC-associated DEmRNAs were adopted to construct the PPI network. The expression of the top 6 genes in the hub module was validated in mRNA transcriptome sequencing data and ICC-related gene expression dataset GSE45001, followed by GO and KEGG pathway enrichment analysis. The potential function of genes in hub module in the ceRNA network was finally subjected to GSEA. Results Sixty coexpression DEmRNAs were identified in the ceRNA network. The 6 top genes in the hub module consists of FOS, HGF, IGF2, FOXO1, NTF3 (downregulated), and IGF1R (upregulated) in ICC tissues compared to normal adjacent tissues, followed by the successful construction of lncRNA-miR-hub network with 86 ceRNA modules. FOS, IGF2 or IGF1R might regulate the development of ICC by targeting “N-glycan biosynthesis”, “α-linolenic acid metabolism” or “type II diabetes” pathways respectively. Conclusion These results show FOS, IGF2 and IGF1R serve as prognostic factors of ICC patients.

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Formation of the IGF1R/CAV1/SRC tri‐complex antagonizes TRAIL‐induced apoptosis in gastric cancer cells

Cited by 11 publications

References 29 publications

Identification of prognostic factors for intrahepatic cholangiocarcinoma using long non-coding RNAs-associated ceRNA network

Identification of prognostic factors for intrahepatic cholangiocarcinoma using long non-coding RNAs-associated ceRNA network

β‐elemene increases the sensitivity of gastric cancer cells to TRAIL by promoting the formation of DISC in lipid rafts

Identification of prognostic factors for intrahepatic cholangiocarcinoma based on long non-coding RNAs-associated ceRNA network

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