OncoTargets and Therapy (Oct 2020)
Yes-Associated Protein Contributes to Cell Proliferation and Migration of Gastric Cancer via Activation of Gli1
Abstract
Ting Han,1 Zhengwu Cheng,1 Menglin Xu,2 Xiaoming Wang,3 Jian Wu,1 Xiaosan Fang3 1Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu 241000, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital of Wannan Medical College, Wuhu 241000, People’s Republic of China; 3Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu 241000, People’s Republic of ChinaCorrespondence: Xiaosan FangDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College, No. 2 Zheshan West Road, Jinghu District, Wuhu 241000, Anhui Province, People’s Republic of ChinaEmail [email protected]: In the present study, we aimed to explore the potential oncogenic property and the internal mechanism of yes-associated protein (YAP) in gastric cancer (GC).Materials and Methods: YAP protein levels were evaluated in human GC tissues and paired normal tissues using immunohistochemistry (IHC). The role of YAP in regulating GC cell proliferation and migration was verified by genetic manipulation in vitro. Western blot analysis was used to determine the molecular signaling to explain the mechanism of the observed YAP effects in GC.Results: Nuclear YAP protein expression was upregulated in GC tissues, and high nuclear YAP level was significantly correlated with lymph node metastasis (LNM) and tumor node metastasis (TNM) stage in patients suffered from GC. YAP knockdown inhibited GC cell proliferation, migration and epithelial–mesenchymal transition (EMT) progress in vitro, whereas YAP elevation did the opposite. YAP regulated glioma-associated oncogene-1 (Gli1) expression independent of smoothened homolog (SMO). YAP modulated protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway in GC cells.Conclusion: YAP enhanced GC cell proliferation and migration potentially via its regulation of Gli1 expression through the non-classical Hedgehog pathway, indicating suppression of YAP/Gli1 signaling axis may highlight a new entry point for combination therapy of GC.Keywords: YAP, proliferation, migration, Hedgehog pathway, gastric cancer
