An ARF GTPase module promoting invasion and metastasis through regulating phosphoinositide metabolism.

ABSTRACT: The signalling pathways underpinning cell growth and invasion use overlapping components, yet how mutually exclusive cellular responses occur is unclear. Here, we report development of 3-Dimensional culture analyses to separately quantify growth and invasion. We identify that alternate variants of IQSEC1, an ARF GTPase Exchange Factor, act as switches to promote invasion over growth by controlling phosphoinositide metabolism. All IQSEC1 variants activate ARF5- and ARF6-dependent PIP5-kinase to promote PI(3,4,5)P₃-AKT signalling and growth. In contrast, select pro-invasive IQSEC1 variants promote PI(3,4,5)P₃ production to form invasion-driving protrusions. Inhibition of IQSEC1 attenuates invasion in vitro and metastasis in vivo. Induction of pro-invasive IQSEC1 variant

SUBMITTER: Nacke M 

PROVIDER: S-EPMC7955138 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature