title: Recombinant viral capsid protein VP1 suppresses migration and invasion of human cervical cancer by modulating phosphorylated prohibitin in lipid rafts.
abstract: Recombinant capsid protein VP1 (rVP1) of foot-and-mouth disease virus inhibits invasion/metastasis of cancer cells. Here we studied its mechanism of action on human cervical cancer cells. The inhibition of cell invasion by rVP1 was accompanied with reduction in phosphatidylinositol (3,4,5)-triphosphate (PIP3), phospho-Akt S473, phosphorylated prohibitin (phospho-PHB) T258 in lipid rafts, dissociation of phospho-PHB T258 with Raf-1 and the inactivation of Raf-1/ERK. Addition of PIP3 or overexpression of constitutively active Akt and raft-anchored PHB T258 but not PHB T258I mutant protein reversed the inhibitory effects of rVP1. rVP1 inhibited cervical tumor growth and metastasis, and prolonged survival in xenograft mouse models. These results suggest that rVP1 inhibits cancer metastasis via de-phosphorylation of Akt and PHB T258 in lipid rafts to downregulate Raf/ERK signaling.
authors.affiliation: Institute of Biotechnology, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Chiu
authors.forename: Jei-Ming
authors.initials: JM
authors.lastname: Peng
authors.forename: Shao-Wen
authors.initials: SW
authors.lastname: Hung
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Liang
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Liang
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D005260:Female; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010766:Phosphorylation; D000091402:Prohibitins; D011994:Recombinant Proteins / Q000494:pharmacology; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology*; D048490:raf Kinases / Q000378:metabolism
chemical_list: D036022:Capsid Proteins; C000717328:PHB protein, human; D018129:Phosphatidylinositol Phosphates; D000091402:Prohibitins; D011994:Recombinant Proteins; D012097:Repressor Proteins; C442501:VP1 protein, Foot-and-mouth disease virus; C060974:phosphatidylinositol 3,4,5-triphosphate; D048490:raf Kinases