title: Distinct roles of Akt1 in regulating proliferation, migration and invasion in HepG2 and HCT 116 cells.
abstract: Elucidating the effects of genes involved in tumors may improve therapeutic strategies for human cancer. Recently, several studies discovered that Akt1 plays a dual role in mediating cell proliferation, migration and invasion, depending on the cell type. However, the pathophysiological role of Akt1 in hepatocellular carcinoma (HCC) and colorectal carcinoma cells remains poorly understood. In the present study, we transfected the Akt1-expressing plasmids into the tumor cells that expressed only low levels of Akt1. The migration and invasion abilities were analyzed in 24-well Boyden chambers. The expression of proteins was detected using western blot analysis. Our results demonstrated that overexpression of Akt1 significantly enhanced the proliferation rates and promoted the colony formation in both HepG2 and HCT 116 cells. When treated with wortmannin, the ability to form colonies was significantly attenuated in both cell lines. Of note, enforced expression of Akt1 induced HepG2 cell migration and invasion; by contrast, upregulation of Akt1 expression suppressed the migration and invasion of HCT 116 cells. Subsequent mechanistic investigations revealed that upregulation of Akt1 markedly induced the expression of Bcl-2 and NF-κB in both types of tumor cells. Notably, we observed a similar increase of MMP2, MMP9, HIF1α and VEGF in HCC cells, whereas Akt1 significantly suppressed the expression of these molecules in colorectal carcinoma cells. These data suggest a dual role for Akt1 in tumor cell migration and invasion and highlight the cell type-specific actions of Akt1 kinases in the regulation of cell motility.
authors.affiliation: Institute of Chemical Biology, Henan University, Kaifeng, Henan 475004, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute of Chemical Biology, Henan University, Kaifeng, Henan 475004, P.R. China.
authors.forename: Qiao-Hui
authors.initials: QH
authors.lastname: Kang
authors.affiliation: Institute of Chemical Biology, Henan University, Kaifeng, Henan 475004, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: The Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng, Henan 475004, P.R. China.
authors.forename: Ya-Hong
authors.initials: YH
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng, Henan 475004, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Institute of Chemical Biology, Henan University, Kaifeng, Henan 475004, P.R. China.
authors.forename: Song-Qiang
authors.initials: SQ
authors.lastname: Xie
authors.affiliation: The Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng, Henan 475004, P.R. China.
authors.forename: Chao-Jie
authors.initials: CJ
authors.lastname: Wang
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D016328:NF-kappa B / Q000096:biosynthesis; D009361:Neoplasm Invasiveness / Q000235:genetics; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D000077191:Wortmannin