Loss of TP53I11 Enhances the Extracellular Matrix-independent Survival by Promoting Activation of AMPK
| Autor: | Tongqian, Xiao, Zhongjuan, Xu, Yuanshuai, Zhou, Hai, Zhang, Junsa, Geng, Yu, Liang, Hong, Qiao, Guangli, Suo |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Epithelial-Mesenchymal Transition
Cell Survival TOR Serine-Threonine Kinases Poly (ADP-Ribose) Polymerase-1 Epithelial Cells AMP-Activated Protein Kinases Cadherins Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Cell Line Extracellular Matrix Neoplasm Proteins Gene Expression Regulation Antigens CD Cell Movement Claudin-1 Cell Adhesion Humans Vimentin Snail Family Transcription Factors Mammary Glands Human Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | IUBMB life. 71(2) |
| ISSN: | 1521-6551 |
| 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 |
| Externí odkaz: |
|
Plný text