Calcium signaling induces a partial EMT

Robert J. Norgard, Jason R. Pitarresi, Ravikanth Maddipati, Nicole M. Aiello-Couzo, David Balli, Jinyang Li, Taiji Yamazoe, Maximilian D. Wengyn, Ian D. Millstein, Ian W. Folkert, Derick N. Rosario-Berrios, Il Kyu Kim, Jared B. Bassett, Riley Payne, Corbett T. Berry, Xiaodong Feng, Kathryn Sun, Michele Cioffi, Priyanka Chakraborty, Mohit Kumar JollyJ. Silvio Gutkind, David Lyden, Bruce D. Freedman, J. Kevin Foskett, Anil K. Rustgi, Ben Z. Stanger

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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.

Original languageEnglish (US)
Article numbere51872
JournalEMBO Reports
Issue number9
StatePublished - Sep 6 2021


  • E-cadherin
  • calcium
  • cellular plasticity
  • partial EMT

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics


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