Title | Calcium signaling induces a partial EMT. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Norgard RJ, Pitarresi JR, Maddipati R, Aiello-Couzo NM, Balli D, Li J, Yamazoe T, Wengyn MD, Millstein ID, Folkert IW, Rosario-Berrios DN, Kim I-K, Bassett JB, Payne R, Berry CT, Feng X, Sun K, Cioffi M, Chakraborty P, Jolly MKumar, J Gutkind S, Lyden D, Freedman BD, J Foskett K, Rustgi AK, Stanger BZ |
Journal | EMBO Rep |
Pagination | e51872 |
Date Published | 2021 Jul 29 |
ISSN | 1469-3178 |
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. |
DOI | 10.15252/embr.202051872 |
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Alternate Journal | EMBO Rep |
PubMed ID | 34324787 |
Grant List | CA236269 / / HHS|NIH|National Cancer Institute (NCI) / CA01369645 / / HHS|NIH|National Cancer Institute (NCI) / CA229803 / / HHS|NIH|National Cancer Institute (NCI) / DK083355 / / HHS|NIH|National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) / DK050306 / / HHS|NIH|National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) / 1K08DK109292 / / HHS|NIH|National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) / / / AGA Research Foundation (The AGA Research Foundation) / CA221094 / / HHS|NIH|NCI|Division of Cancer Epidemiology and Genetics, National Cancer Institute (DCEG) / RR190029 / / CPRIT / |