Affiliation: Indian Institute of Technology Kanpur, India
Keywords: a. cytoskeleton; h. tumorigenesis
The cytoskeleton is an essential regulator of cell shape and size changes, of which microtubules (MT) are a crucial component. Indeed, MT re-organize during epithelial cell shape transition, for instance, from columnar to the squamous cell shape. The mechanism that regulates these MT-mediated cell shape remodeling, however, is not known. Here, we show that MT acetylation is an essential step during epithelial cell stretching. For instance, MT acetylation increases remarkably during columnar-to-squamous transition. Conversely, loss of MT acetylation via genetic downregulation of Tubulin Acetyl Transferase (TAT) compromises the cell stretching by dysregulating the turnover of polarity protein, Crumbs, and cell-cell adhesion protein, cadherin. We further show that neoplastic transformation of squamous epithelium is accompanied by hyperacetylation of MT. Our results, therefore, reveal an essential mechanism of MT-acetylation-dependent cell shape regulation as well as squamous cell carcinogenesis and hints at potential therapeutic targets.