title: Hes1 promotes cell proliferation and migration by activating Bmi-1 and PTEN/Akt/GSK3β pathway in human colon cancer.
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.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou 510515, China.
authors.forename: YuQin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
authors.forename: ShaoHui
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ma
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou 510515, China.
authors.forename: YiMing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Clinical Experimental Center, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D000072056:Transcription Factor HES-1; D014162:Transfection
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D018398:Homeodomain Proteins; D051059:PTEN Phosphohydrolase; D063150:Polycomb Repressive Complex 1; D051057:Proto-Oncogene Proteins c-akt; D000072056:Transcription Factor HES-1; C069077:BMI1 protein, human; C078493:HES1 protein, human; C000605506:GSK3B protein, human; C494929:PTEN protein, human
keywords: Bmi-1; Hes1; PTEN; colon cancer; metastasis