Calcium signaling induces a partial EMT.

TitleCalcium signaling induces a partial EMT.
Publication TypeJournal Article
Year of Publication2021
AuthorsNorgard 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
JournalEMBO Rep
Date Published2021 Jul 29

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.

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Alternate JournalEMBO Rep
PubMed ID34324787
Grant ListCA236269 / / 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 /

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