Calcium signaling induces a partial EMT. Academic Article uri icon

Overview

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.

publication date

  • July 29, 2021

Research

keywords

  • Calcium Signaling
  • Epithelial-Mesenchymal Transition

Identity

PubMed Central ID

  • PMC8419705

Scopus Document Identifier

  • 85111552870

Digital Object Identifier (DOI)

  • 10.1101/2020.04.18.047803

PubMed ID

  • 34324787

Additional Document Info

volume

  • 22

issue

  • 9