Open AccessNANOG regulates epithelial–mesenchymal transition via AMPK / mTOR signalling pathway in ovarian cancer SKOV ‐3 and A2780 cells
Author(s) -
Yun Hee,
Han Gwan Hee,
Kim Julie,
Chung JoonYong,
Kim JaeHoon,
Cho Hanbyoul
Publication year - 2022
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.17557
Subject(s) - homeobox protein nanog , epithelial–mesenchymal transition , cancer research , sox2 , ampk , metastasis , ovarian cancer , nanog homeobox protein , gene knockdown , pi3k/akt/mtor pathway , biology , cancer , medicine , signal transduction , transcription factor , cell culture , microbiology and biotechnology , embryonic stem cell , kinase , protein kinase a , induced pluripotent stem cell , biochemistry , genetics , gene
NANOG engages with tumour initiation and metastasis by regulating the epithelial–mesenchymal transition (EMT) in epithelial ovarian cancer (EOC). However, its role in association with pAMPKα, and its clinical significance in EOC have not been elucidated even though AMPK is known to degrade NANOG in various human cancers. Hence, we investigated the role of pAMPKα and its association with NANOG as potential prognostic biomarkers in EOC. Both NANOG and pAMPKα expression were significantly overexpressed in EOCs comparing nonadjacent normal epithelial tissues, benign tissues, and borderline tumours. NANOG overexpression was significantly associated with poor disease‐free survival (DFS) and overall survival (OS), whereas pAMPKα overexpression was associated with good DFS and OS. Importantly, multivariate analysis revealed that the combination of high NANOG and low pAMPKα expression was a poor independent prognostic factor for DFS and was associated with platinum resistance. In ovarian cancer cell lines, siRNA‐mediated NANOG knockdown diminished migration and invasion properties by regulating the EMT process via the AMPK/mTOR signalling pathway. Furthermore, treatment with AMPK activator suppressed expression of stemness factors such as NANOG, Oct4 and Sox2. Collectively, these findings established that the combination of high NANOG and low pAMPKα expression was associated with EOC progression and platinum resistance, suggesting a potential prognostic biomarker for clinical management in EOC patients.