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.
Keywords:
AKT; AMPK; ECM-independent survival; TP53I11; migration.
© 2018 International Union of Biochemistry and Molecular Biology.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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AMP-Activated Protein Kinases / genetics*
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AMP-Activated Protein Kinases / metabolism
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Antigens, CD / genetics
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Antigens, CD / metabolism
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Cadherins / genetics
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Cadherins / metabolism
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Cell Adhesion
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Cell Line
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Cell Movement
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Cell Survival
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Claudin-1 / genetics
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Claudin-1 / metabolism
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Epithelial Cells / cytology
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Epithelial Cells / metabolism
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Epithelial-Mesenchymal Transition / genetics*
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Extracellular Matrix / chemistry
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Extracellular Matrix / metabolism*
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Gene Expression Regulation
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Humans
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Mammary Glands, Human / cytology
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Mammary Glands, Human / metabolism
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Neoplasm Proteins / deficiency
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Neoplasm Proteins / genetics*
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
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Poly (ADP-Ribose) Polymerase-1 / genetics*
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Poly (ADP-Ribose) Polymerase-1 / metabolism
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Proto-Oncogene Proteins c-akt / genetics*
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Proto-Oncogene Proteins c-akt / metabolism
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Signal Transduction
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Snail Family Transcription Factors / genetics
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Snail Family Transcription Factors / metabolism
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TOR Serine-Threonine Kinases / genetics
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TOR Serine-Threonine Kinases / metabolism
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Vimentin / genetics
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Vimentin / metabolism
Substances
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Antigens, CD
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CDH1 protein, human
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CLDN1 protein, human
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Cadherins
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Claudin-1
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Neoplasm Proteins
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PPARGC1A protein, human
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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SNAI1 protein, human
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Snail Family Transcription Factors
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TP53I11 protein, human
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VIM protein, human
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Vimentin
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PARP1 protein, human
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Poly (ADP-Ribose) Polymerase-1
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MTOR protein, human
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Proto-Oncogene Proteins c-akt
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TOR Serine-Threonine Kinases
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AMP-Activated Protein Kinases