Recombinant viral capsid protein VP1 suppresses migration and invasion of human cervical cancer by modulating phosphorylated prohibitin in lipid rafts

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 5473, phosphorylated prohibitin (phospho-PHB) T258 in lipid rafts, dissociation of phospho-PHB 1258 with Raf-1 and the inactivation of Raf-1/ERK. Addition of PIP3 or overexpression of constitutively active Akt and raft-anchored PHB 1258 but not PHB 12581 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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.