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Calcium signaling induces a partial EMT
Author(s) -
Norgard Robert J,
Pitarresi Jason R,
Maddipati Ravikanth,
AielloCouzo Nicole M,
Balli David,
Li Jinyang,
Yamazoe Taiji,
Wengyn Maximilian D,
Millstein Ian D,
Folkert Ian W,
RosarioBerrios Derick N,
Kim IlKyu,
Bassett Jared B,
Payne Riley,
Berry Corbett T,
Feng Xiaodong,
Sun Kathryn,
Cioffi Michele,
Chakraborty Priyanka,
Jolly Mohit Kumar,
Gutkind J Silvio,
Lyden David,
Freedman Bruce D,
Foskett J Kevin,
Rustgi Anil K,
Stanger Ben Z
Publication year - 2021
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202051872
Subject(s) - library science , medicine , gerontology , cancer , family medicine , computer science
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.