Loss of TP53I11 Enhances the Extracellular Matrix‐independent Survival by Promoting Activation of AMPK. Issue 2 (30th October 2018)

• Record Type: Journal Article
• Authors: Xiao, Tongqian; Xu, Zhongjuan; Zhou, Yuanshuai; Zhang, Hai; Geng, Junsa; Liang, Yu; Qiao, Hong; Suo, Guangli
• Is Part Of: IUBMB life. Volume 71:Issue 2(2019)
• Page Start: 183
• Page End: 191
• Publication Date: 2018-10-30
• Subjects: TP53I11 -- ECM‐independent survival -- AKT -- AMPK -- migration; Biochemistry -- Periodicals; Molecular biology -- Periodicals; 572.8
• DOI: 10.1002/iub.1949
• Languages: English
• ISSNs: 1521-6543

Abstract

Abstract: Extracellular matrix (ECM)‐independent survival is an essential prerequisite for tumor metastasis, and a hallmark of epithelial cancer stem cells and epithelial–mesenchymal transition (EMT). Here, we found that loss of TP53I11 enhanced, and overexpression of TP53I11 suppressed the ECM‐independent survival, EMT, and migration in MCF10A cells. TP53I11 has long been considered as a transcriptional target of TP53. However, we found that TP53I11 regulated the ECM‐independent survival by a TP53‐independent way. As a metabolic sensor, AMPK promoted anoikis resistance by inhibiting AKT/m‐TOR/p70S6K signaling pathway. It was recently revealed that the reciprocal inhibitory relationship between AKT and AMPK regulated adaptation of cells to ECM‐detachment. Our results demonstrated that loss of TP53I11 promoted the activation of AKT/m‐TOR pathway, increased PGC‐1α expression and thereby enhanced OXPHOS in attach‐cultured MCF10A cells, but promoted AMPK activation to inhibit AKT/m‐TOR/p70S6K signaling pathway in detach‐cultured MCF10A cells. This indicates that TP53I11 functions as a mediator to balance activation of AKT and AMPK to adapt cells to different cellular contexts such as ECM‐attachment and ‐detachment. © 2018 IUBMB Life, 71(1):183–191, 2019