Open AccessUp‐regulated acylglycerol kinase (AGK) expression associates with gastric cancer progression through the formation of a novel YAP1‐AGK–positive loop
Author(s) -
Huang Shanshan,
Cao Yuan,
Guo Hui,
Yao Yangyang,
Li Li,
Chen Jun,
Li Junhe,
Xiang Xiaojun,
Deng Jun,
Xiong Jianping
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15613
Subject(s) - yap1 , biology , cancer cell , cancer , carcinogenesis , cancer research , gene knockdown , cell growth , hippo signaling pathway , microbiology and biotechnology , transcription factor , kinase , cell culture , biochemistry , gene , genetics
Acylglycerol kinase (AGK) uses adenosine triphosphate (ATP) and acylglycerol to generate adenosine diphosphate (ADP) and acyl‐sn‐glycerol 3‐phosphate in cells. Recent evidence has demonstrated that dysregulated AGK expression is associated with the development of various human cancers. This study investigated the effects of AGK on gastric cancer cell proliferation and carcinogenesis and explored the underlying molecular events. AGK expression was up‐regulated in gastric cancer and was associated with poor prognosis in gastric cancer patients. AGK overexpression increased gastric cancer proliferation, invasion capacity and the expression of the epithelial‐mesenchymal transition markers in vitro. Conversely, the knockdown of AGK expression reduced gastric cancer cell proliferation in vitro and in nude mouse tumour cell xenografts. Importantly, AGK expression was associated with the YAP1 expression in gastric cancer cells and tissues. YAP1 expression also transcriptionally induced AGK expression through the binding of TEAD to the AGK gene promoter. However, AGK expression inhibited the activation of the Hippo pathway proteins and induced YAP1 nuclear localization to enhance the transcription activity of YAP1/TEADs. In conclusion, the study demonstrates that AGK is not only a novel target of the Hippo‐YAP1 pathway, but that it also positively regulates YAP1 expression, thus forming a YAP1‐AGK–positive feedback loop.