Hes1 promotes cell proliferation and migration by activating Bmi-1 and PTEN/Akt/GSK3β pathway in human colon cancer
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Fei Gao1, Wei Huang1, YuQin Zhang3, ShaoHui Tang1, Lin Zheng5, Feng Ma1, YiMing Wang3, Hui Tang4, Xin Li2
1Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China
2Cancer Research Institute, Southern Medical University, Guangzhou 510515, China
3Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou 510515, China
4Clinical Experimental Center, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China
5Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
Fei Gao, e-mail: [email protected]
Xin Li, e-mail: [email protected]
Keywords: Hes1, Bmi-1, PTEN, metastasis, colon cancer
Received: June 18, 2015 Accepted: September 25, 2015 Published: October 6, 2015
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.
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