title: MEK/ERK pathway is positively involved in hypoxia-induced vasculogenic mimicry formation in hepatocellular carcinoma which is regulated negatively by protein kinase A.
abstract: The aim of present investigation is to explore the molecular mechanisms of vasculogenic mimicry (VM) induced by hypoxia. Hepatocellular carcinoma cell lines were treated with CoCl2, and the VM-related parameters were assayed by real-time qPCR, Western blotting and immunofluorescence. Matrigel tube structure was also detected. We demonstrated that the expression of pMEK, MEK, pERK1/2 and ERK1/2 had a positive correlation with VM induced by hypoxia in MHCC97H while HepG2 signified VM under normoxia condition. PD98059 was negatively while epidermal growth factor positively participated in the increased tubes and area of VM. At the meaning time, the increased VM-related genes VE-cadherin, MMP2, MMP9, EphA2 and LAMC2 in hypoxia group were down-regulated by PD98059 in a dose-dependent manner. Furthermore, we elucidated that PKA, but not PKC, mediated the MEK/ERK pathway in a negative manner in VM. In conclusion, MEK/ERK pathway is positively involved in VM in hepatocellular carcinoma cell line, which was mediated by PKA negatively.
authors.affiliation: Radiology Department, The Second Xiangya Hospital of Central South University, No. 139, Renmin Road, Changsha, 410008, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Huang
authors.forename: Enhua
authors.initials: E
authors.lastname: Xiao
authors.forename: Manping
authors.initials: M
authors.lastname: Huang
mesh_terms: D000067558:Biological Mimicry; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017868:Cyclic AMP-Dependent Protein Kinases