Abstract 2014: CAMSAP3, a tubulin minus-end binding protein, attenuates epithelial-to-mesenchymal transition and alters microtubule dynamic in non-small cell lung cancer

Abstract

Abstract Cancer metastasis become the major cause of mortality in cancer patients, which the cancer migration exerts this aggressiveness. Epithelial to mesenchymal transition (EMT) plays an important role on cell movement and survival of the cancer cells during metastasizes. The establishment of front-rare polarization is involved with the alteration of cytoskeleton and cell-cell interaction, contributing to the notable morphological transformation from cobble stone-like epithelial to fibroblast-like mesenchymal feature. Microtubule dynamic has gained attention as a modulator behind these phenotypic changes and the EMT-related signal trafficking. Tubulin behavior has been shown to be governed by microtubule-binding proteins including a family of Calmodulin-regulated spectrin-associated proteins (CAMSAPs), a tubulin minus-end binding proteins. To illustrate the role of CAMSAPs on mesenchymal transition, CAMSAP2 and 3 genes were knockout using CRISPR-Cas9 system. Wound scratching and transwell migration assays demonstrate that non-small cell lung cancer becomes more motile with an elevation of actin stress fiber and focal adhesion protein paxillin following CAMSAP3 knockout, whereas CAMSAP2 depletion shows no significant effect. The mesenchymal markers including Slug, N-Cadherin and ZEB1 were substantial up-regulated, in opposite to the epithelial marker E-cadherin. Furthermore, CAMSAP3 removal causes a decrease of tubulin dynamic and consequently sustains an active state of EMT-regulatory proteins. This study reveals the negative regulatory effect of CAMSAP3, a non-centrosomal microtubule minus-end binding protein, on mesenchymal transition and cell motility. Citation Format: Varisa Pongrakhananon, Onsurang Wattanathamsan, Masatoshi Takeichi. CAMSAP3, a tubulin minus-end binding protein, attenuates epithelial-to-mesenchymal transition and alters microtubule dynamic in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2014.