Open AccessLoss of CAMSAP3 promotes EMT via the modification of microtubule-Akt machinery
Author(s) -
Varisa Pongrakhana,
Onsurang Wattanathamsan,
Masatoshi Takeichi,
Paninee Chetprayoon,
Pithi Chanvorachote
Publication year - 2018
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.216168
Subject(s) - microtubule , biology , downregulation and upregulation , microbiology and biotechnology , epithelial–mesenchymal transition , protein kinase b , acetylation , cytoskeleton , tubulin , phenotype , cancer research , signal transduction , cell , genetics , gene
Epithelial-to-mesenchymal transition (EMT) plays pivotal roles in a variety of biological processes, including cancer invasion. EMT involves alterations of cytoskeletal proteins, including microtubules. The role of microtubules in EMT, however, 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 CAMSAP3 in human lung carcinoma-derived cell lines showed that CAMSAP3-deficient cells acquired increased mesenchymal features mostly at transcriptional levels. Analysis of the mechanisms underlying these changes showed that tubulin acetylation was dramatically increased following CAMSAP3 removal, leading to the upregulation of protein kinase B/Akt activity, which is known to promote EMT. These findings suggested 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.