YAP‐TEAD up‐regulates IRS2 expression to induce and deteriorate oesophageal cancer
Copyright policy )YAP‐TEAD up‐regulates IRS2 expression to induce and deteriorate oesophageal cancer
AbstractOesophageal cancer (EC) represents a significant cause of cancer worldwide. Yes‐associated protein (YAP) is reported to correlate with the initiation of multiple cancers including EC, but the underlying mechanism remains elusive. The current study aimed to investigate the molecular mechanism of YAP‐TEAD in the occurrence and progression of EC. EC tissues and cells were obtained, followed by determination of the expression of YAP, c‐Jun, pc‐Jun and IRS2. The effect of YAP‐TEAD on the biological EC cell processes was explored through gain‐ and loss‐of‐function approaches. The interaction between YAP and TEAD was detected by co‐immunoprecipitation. The binding of TEAD to the c‐Jun promoter was determined using chromatin immunoprecipitation. Tumour formation in the nude mice was detected in order to ascertain the effect of YAP and IRS2 in vivo. We found elevated YAP in the EC tissues and cells. YAP silencing led to a decrease in EC cell proliferation, invasion and sphere formation. YAP‐TEAD complex bound to the promotor of c‐Jun, and c‐Jun led to an increase in the expression of IRS2 through the JNK/c‐Jun pathway. Additionally, pc‐Jun and phosphorylated JNK were localized in the nuclear in addition to displaying enhanced expression in the EC tissues. IRS2 overexpression negated the inhibition of cell proliferation, invasion and sphere formation triggering YAP silencing. YAP up‐regulated IRS2 and aggravated EC in vivo. Taken together, YAP‐TEAD activates the JNK/c‐Jun pathway to up‐regulate IRS2, ultimately promoting EC progression. Therefore, YAP‐TEAD inhibition could be a promising therapeutic approach for EC treatment.
- Linyi People's Hospital China (People's Republic of)
Male, Esophageal Neoplasms, MAP Kinase Signaling System, Cell Cycle Proteins, Original Articles, Immunohistochemistry, Models, Biological, Gene Expression Regulation, Neoplastic, Disease Models, Animal, Mice, Cell Line, Tumor, Insulin Receptor Substrate Proteins, Animals, Humans, Gene Silencing, Protein Binding, Signal Transduction, Transcription Factors
Male, Esophageal Neoplasms, MAP Kinase Signaling System, Cell Cycle Proteins, Original Articles, Immunohistochemistry, Models, Biological, Gene Expression Regulation, Neoplastic, Disease Models, Animal, Mice, Cell Line, Tumor, Insulin Receptor Substrate Proteins, Animals, Humans, Gene Silencing, Protein Binding, Signal Transduction, Transcription Factors
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