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

Fei Gao; Wei Huang; YuQin Zhang; ShaoHui Tang; Lin Zheng; Feng Ma; YiMing Wang; Hui Tang; Xin Li

doi:10.18632/oncotarget.5484

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

Oncotarget. 2015 Nov 17;6(36):38667-80. doi: 10.18632/oncotarget.5484.

Authors

Fei Gao¹, Wei Huang¹, YuQin Zhang², ShaoHui Tang¹, Lin Zheng³, Feng Ma¹, YiMing Wang², Hui Tang⁴, Xin Li⁵

Affiliations

¹ Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
² Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou 510515, China.
³ Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
⁴ Clinical Experimental Center, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
⁵ Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.

Abstract

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.

Keywords: Bmi-1; Hes1; PTEN; colon cancer; metastasis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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
PTEN Phosphohydrolase / metabolism
Polycomb Repressive Complex 1 / biosynthesis
Polycomb Repressive Complex 1 / genetics
Polycomb Repressive Complex 1 / metabolism*
Proto-Oncogene Proteins c-akt / metabolism
Signal Transduction
Transcription Factor HES-1
Transfection

Substances

BMI1 protein, human
Basic Helix-Loop-Helix Transcription Factors
Homeodomain Proteins
Transcription Factor HES-1
HES1 protein, human
Polycomb Repressive Complex 1
GSK3B protein, human
Glycogen Synthase Kinase 3 beta
Proto-Oncogene Proteins c-akt
Glycogen Synthase Kinase 3
PTEN Phosphohydrolase
PTEN protein, human