Sec8 regulates cytokeratin8 phosphorylation and cell migration by controlling the ERK and p38 MAPK signalling pathways

Cell migration is involved in numerous biological processes, including morphogenesis, wound healing and inflammatory responses, and is regulated by harmonic modulations of cellular cytoskeletal elements. The intermediate filament cytokeratin8 is one cytoskeletal element that has been implicated in cell migration. Sec8 is a component of an exocyst complex and is associated with various phenomena, such as cell migration, invadopodia formation, cytokinesis, glucose uptake and neural development. However, the relationship between Sec8 and cytokeratin8 remains to be elucidated. In this study, depleting Sec8 in HSC3 cells suppressed their migration by controlling the phosphorylation of cytokeratin8 at Ser73. This reduced cytokeratin8 phosphorylation at Ser73 is regulated by the activation of ERK and p38 mitogen-activated protein kinases (MAPK) signalling pathways via the downregulation of p21-activated kinases by p53-induced RING-H2 (Pirh2) and seven-in-absentia homologue 1 (Siah1) under conditions of Sec8 knockdown. (C) 2015 Elsevier Inc. All rights reserved.