Loss of TP53I11 Enhances the Extracellular Matrix-independent Survival by Promoting Activation of AMPK
| Autor: | Guangli Suo, Yuanshuai Zhou, Tongqian Xiao, Junsa Geng, Hong Qiao, Zhongjuan Xu, Yu Liang, Hai Zhang |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Chemistry Clinical Biochemistry AMPK Cell Biology Oxidative phosphorylation medicine.disease Biochemistry Metastasis Cell biology Extracellular matrix 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Mediator 030220 oncology & carcinogenesis Genetics medicine Stem cell Signal transduction Molecular Biology Protein kinase B |
| Zdroj: | IUBMB Life. 71:183-191 |
| ISSN: | 1521-6543 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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