RITA modulates cell migration and invasion by affecting focal adhesion dynamics.

Samira Catharina Hoock,Susanne Roth,Andreas Ritter,Christian Behrends,Christine Solbach,Nina‐Naomi Kreis,Juping Yuan,Frank Louwen,Franz Oswald,Kerstin Steinhäuser

doi:10.1002/1878-0261.12551

Samira Catharina Hoock, Susanne Roth + Show 8 more

Open Access

https://doi.org/10.1002/1878-0261.12551

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Abstract

RITA, the RBP‐J interacting and tubulin‐associated protein, has been reported to be related to tumor development, but the underlying mechanisms are not understood. Since RITA interacts with tubulin and coats microtubules of the cytoskeleton, we hypothesized that it is involved in cell motility. We show here that depletion of RITA reduces cell migration and invasion of diverse cancer cell lines and mouse embryonic fibroblasts. Cells depleted of RITA display stable focal adhesions (FA) with elevated active integrin, phosphorylated focal adhesion kinase, and paxillin. This is accompanied by enlarged size and disturbed turnover of FA. These cells also demonstrate increased polymerized tubulin. Interestingly, RITA is precipitated with the lipoma‐preferred partner (LPP), which is critical in actin cytoskeleton remodeling and cell migration. Suppression of RITA results in reduced LPP and α‐actinin at FA leading to compromised focal adhesion turnover and actin dynamics. This study identifies RITA as a novel crucial player in cell migration and invasion by affecting the turnover of FA through its interference with the dynamics of actin filaments and microtubules. Its deregulation may contribute to malignant progression.

Highlights

Aberrant cell migration contributes to cancer metastasis responsible for over 90% of cancer associated deaths (Chaffer and Weinberg, 2011)
Cell migration is precisely regulated by a controlled turnover of cellular anchors characterized by four distinct events: leading edge protrusion with dynamic actin polymerization, Abbreviations focal adhesions (FA), focal adhesion; F-actin, filamentous actin; LPP, lipoma-preferred partner; MEFs, mouse embryonic fibroblasts; MT, microtubule; RITA, RBP-J-interacting and tubulin-associated protein
We show that knockdown of RITA impairs FA dynamics leading to decreased migration and invasion of diverse cancer cell lines as well as mouse embryonic fibroblasts (MEF)

Summary

Introduction

Aberrant cell migration contributes to cancer metastasis responsible for over 90% of cancer associated deaths (Chaffer and Weinberg, 2011). Cell migration is precisely regulated by a controlled turnover of cellular anchors characterized by four distinct events: leading edge protrusion with dynamic actin polymerization, Abbreviations FA, focal adhesion; F-actin, filamentous actin; LPP, lipoma-preferred partner; MEFs, mouse embryonic fibroblasts; MT, microtubule; RITA, RBP-J-interacting and tubulin-associated protein. The most common forms are focal adhesions (FA), composed of 232 different proteins forming the integrin adhesome network with over 6500 interactions demonstrating its complexity (WinogradKatz et al, 2014). Integrins transduce signals through co-clustering and recruitment of numerous scaffolding proteins including the cytoplasmic nonreceptor tyrosine kinase focal adhesion kinase (FAK), which regulates intracellular pathways like migration (Guo and Giancotti, 2004). Since the underlying mechanisms are not completely understood, elucidation of the regulation of FA dynamics by MT-associated proteins (MAPs) will extend and refine the understanding of cancer cell migration and metastasis

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