Loss of CAMSAP3 promotes EMT via the modification of microtubule-Akt machinery.

Epithelial-to-mesenchymal transition (EMT) plays pivotal roles in a variety of biological processes, including cancer invasion. Although EMT involves alterations of cytoskeletal proteins such as microtubules, the role of microtubules in EMT is not fully understood. Microtubule dynamics are regulated by microtubule-binding proteins, and one such protein is CAMSAP3, which binds the minus-end of microtubules. Here, we show that CAMSAP3 is important to preserve the epithelial phenotypes in lung carcinoma cells. Deletion of in human lung carcinoma-derived cell lines showed that CAMSAP3-deficient cells acquired increased mesenchymal features, mostly at the transcriptional level. Analysis of the mechanisms underlying these changes demonstrated that tubulin acetylation was dramatically increased following CAMSAP3 removal, leading to the upregulation of Akt proteins (also known as protein kinase B proteins, hereafter Akt) activity, which is known to promote EMT. These findings suggest that CAMSAP3 functions to protect lung carcinoma cells against EMT by suppressing Akt activity via microtubule regulation and that CAMSAP3 loss promotes EMT in these cells.This article has an associated First Person interview with the first author of the paper.