YAP promotes the proliferation and migration of colorectal cancer cells through the Glut3/AMPK signaling pathway

Linhua Jiang; Jiawen Zhang; Qixuan Xu; Bin Wang; Yizhou Yao; Liang Sun; Xuchao Wang; Diyuan Zhou; Ling Gao; Shiduo Song; Xinguo Zhu

doi:10.3892/ol.2021.12573

YAP promotes the proliferation and migration of colorectal cancer cells through the Glut3/AMPK signaling pathway

Oncol Lett. 2021 Apr;21(4):312. doi: 10.3892/ol.2021.12573. Epub 2021 Feb 23.

Authors

Linhua Jiang¹, Jiawen Zhang¹, Qixuan Xu¹, Bin Wang¹, Yizhou Yao¹, Liang Sun¹, Xuchao Wang¹, Diyuan Zhou¹, Ling Gao¹, Shiduo Song¹, Xinguo Zhu¹

Affiliation

¹ Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.

Abstract

Yes-associated protein (YAP), as a major downstream effector in the Hippo signaling pathway, is considered as an oncogene in cancer. The present study aimed to investigate the potential role of YAP in the development and progression of colorectal cancer (CRC). The mRNA and protein expression levels of YAP in human CRC tissue samples and adjacent normal tissue were analyzed using public databases, as well as clinical samples. The potential roles of YAP and the underlying mechanism regulating the proliferation and migration of CRC cells were examined using genetic manipulation in vitro. The correlation between the expression of the YAP gene and epithelial-to-mesenchymal transition (EMT) markers was investigated in order to determine the mechanism underlying the observed effects of YAP. YAP mRNA expression levels were significantly upregulated in CRC tissue compared with in normal tissue, as determined using datasets obtained from Oncomine. Similarly, in clinical samples, the protein expression levels of YAP were significantly upregulated in CRC tissue samples compared with in normal tissue samples. YAP knockdown inhibited the proliferation and migration of CRC cells in vitro, whereas its overexpression resulted in the opposite effect. The expression levels of the YAP gene were positively correlated with those of EMT markers (such as vimentin and N-cadherin) and EMT-inducing transcription factors (such as Snail1, Slug and zinc finger E-box binding homeobox 1 and 2) in CRC samples from Gene Expression Profiling Interactive Analysis. Furthermore, YAP silencing increased the protein expression of E-cadherin and decreased that of vimentin in CRC cells. By contrast, the overexpression of YAP had the opposite effect. YAP promoted the glucose transporter 3 (Glut3)/AMP-activated protein kinase (AMPK) signaling pathway in CRC cells. In conclusion, YAP promoted the proliferation and migration of CRC cells, as well as the expression of EMT markers, possibly by regulating the Glut3/AMPK signaling pathway.

Keywords: Yes-associated protein; colorectal cancer; epithelial-to-mesenchymal-transition; migration; proliferation.

Grants and funding

The present study was supported by the Project of National Science Foundation of Jiangsu Province of China (grant no. BK20161225) and the Project of Science and Technology Plan of Suzhou of China (grant no. SYS2019050).