RITA modulates cell migration and invasion by affecting focal adhesion dynamics.
Mol Oncol. 2019 Jul 28. doi: 10.1002/1878-0261.12551. [Epub ahead of print]
|Authors/Editors:||Hoock SC, Ritter A, Steinhäuser K, Roth S, Behrends C, Oswald F, Solbach C, Louwen F, Kreis NN, Yuan J.|
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 with elevated active integrin, phosphorylated focal adhesion kinase and paxillin. This is accompanied by enlarged size and disturbed turnover of focal adhesions. 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 focal adhesions 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 focal adhesions through its interference with the dynamics of actin filaments and microtubules. Its deregulation may contribute to malignant progression.