BNIP-2 AS A SCAFFOLD FOR GEF-HI/RHOA ACTIVATION IN CANCER CELL MIGRATION

Abstract

Rho small GTPases regulate cytoskeleton dynamics in cell migration during embryonic development, wound healing and immune responses whereas deregulation of this process could lead to pathological states such as cancer cell metastasis. Earlier work from our group has shown that BNIP-2 and Cdc42GAP Homology (BCH) domain controls cell motility and cytoskeleton dynamics via interaction with small GTPases and their regulators GEFs and GAPs. Specifically, BNIP-2 is a BCH domain-containing scaffold protein that interacts with RhoA and has a potential role in regulating cancer cell migration. In this work, I present evidence using stable knockdown, mutants and identification of novel partners to support that BNIP-2 acts as a functional scaffold to promote RhoA signalling in 3D and collective cancer cell migration. The significance of this novel signalling axis is discussed.