1. Calcium signaling induces a partial EMT.
- Author
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Norgard, Robert, Pitarresi, Jason, Maddipati, Ravikanth, Aiello-Couzo, Nicole, Balli, David, Li, Jinyang, Yamazoe, Taiji, Wengyn, Maximilian, Millstein, Ian, Folkert, Ian, Rosario-Berrios, Derick, Kim, Il-Kyu, Bassett, Jared, Payne, Riley, Berry, Corbett, Feng, Xiaodong, Sun, Kathryn, Cioffi, Michele, Chakraborty, Priyanka, Jolly, Mohit, Gutkind, J, Lyden, David, Freedman, Bruce, Foskett, J, Rustgi, Anil, and Stanger, Ben
- Subjects
E-cadherin ,calcium ,cellular plasticity ,partial EMT ,Cadherins ,Calcium Signaling ,Cell Line ,Tumor ,Cell Movement ,Cell Plasticity ,Epithelial-Mesenchymal Transition - Abstract
Epithelial plasticity, or epithelial-to-mesenchymal transition (EMT), is a well-recognized form of cellular plasticity, which endows tumor cells with invasive properties and alters their sensitivity to various agents, thus representing a major challenge to cancer therapy. It is increasingly accepted that carcinoma cells exist along a continuum of hybrid epithelial-mesenchymal (E-M) states and that cells exhibiting such partial EMT (P-EMT) states have greater metastatic competence than those characterized by either extreme (E or M). We described recently a P-EMT program operating in vivo by which carcinoma cells lose their epithelial state through post-translational programs. Here, we investigate the underlying mechanisms and report that prolonged calcium signaling induces a P-EMT characterized by the internalization of membrane-associated E-cadherin (ECAD) and other epithelial proteins as well as an increase in cellular migration and invasion. Signaling through Gαq-associated G-protein-coupled receptors (GPCRs) recapitulates these effects, which operate through the downstream activation of calmodulin-Camk2b signaling. These results implicate calcium signaling as a trigger for the acquisition of hybrid/partial epithelial-mesenchymal states in carcinoma cells.
- Published
- 2021