Hes1 promotes cell proliferation and migration by activating Bmi-1 and PTEN/Akt/GSK3β pathway in human colon cancer

Hes1 is a transcription factor that influences cell proliferation and differentiation. However, the effect of Hes1 on invasiveness and the underlying mechanism remain unknown. In the current study, we found that Hes1 suppressed cell apoptosis, promoted cell growth, induced EMT phenotype and cytoskel...

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Published in:Oncotarget 2015-11, Vol.6 (36), p.38667-38680
Main Authors: Gao, Fei, Huang, Wei, Zhang, YuQin, Tang, ShaoHui, Zheng, Lin, Ma, Feng, Wang, YiMing, Tang, Hui, Li, Xin
Format: Article
Language:English
Subjects:
Basic Helix-Loop-Helix Transcription Factors - biosynthesis
Basic Helix-Loop-Helix Transcription Factors - genetics
Basic Helix-Loop-Helix Transcription Factors - metabolism
Cell Movement - physiology
Cell Proliferation - physiology
Colonic Neoplasms - genetics
Colonic Neoplasms - metabolism
Colonic Neoplasms - pathology
Epithelial-Mesenchymal Transition
Glycogen Synthase Kinase 3 - genetics
Glycogen Synthase Kinase 3 - metabolism
Glycogen Synthase Kinase 3 beta
Homeodomain Proteins - biosynthesis
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Humans
Neoplasm Invasiveness
Neoplasm Metastasis
Polycomb Repressive Complex 1 - biosynthesis
Polycomb Repressive Complex 1 - genetics
Polycomb Repressive Complex 1 - metabolism
Proto-Oncogene Proteins c-akt - metabolism
PTEN Phosphohydrolase - metabolism
Research Paper
Signal Transduction
Transcription Factor HES-1
Transfection
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Summary:Hes1 is a transcription factor that influences cell proliferation and differentiation. However, the effect of Hes1 on invasiveness and the underlying mechanism remain unknown. In the current study, we found that Hes1 suppressed cell apoptosis, promoted cell growth, induced EMT phenotype and cytoskeleton reconstruction, and enhanced the metastatic potential of colon cancer cells in vitro and in vivo. Furthermore, we indicated that Bmi-1 mediated Hes1-induced cell proliferation and migration, downregulated PTEN and activated the Akt/GSK3β pathway, consequently induced EMT and cytoskeleton reconstruction, ultimately leading to enhanced invasiveness of cancer cells. In addition, we also found that both Hes1 and Bmi-1 could directly regulate PTEN by associating at the PTEN locus, and played important roles in regulating PTEN/Akt/GSK3β pathway. Our results provide functional and mechanistic links between Hes1 and Bmi-1/PTEN/Akt/GSK3β signaling in the development and progression of colon cancer.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.5484