Affiliation:
1. Department of Biological Sciences Ulsan National Institute of Science and Technology Ulsan 44919 Republic of Korea
Abstract
AbstractEntosis is a non‐apoptotic cell death process that forms characteristic cell‐in‐cell structures in cancers, killing invading cells. Intracellular Ca2+ dynamics are essential for cellular processes, including actomyosin contractility, migration, and autophagy. However, the significance of Ca2+ and Ca2+ channels participating in entosis is unclear. Here, it is shown that intracellular Ca2+ signaling regulates entosis via SEPTIN‐Orai1‐Ca2+/CaM‐MLCK‐actomyosin axis. Intracellular Ca2+ oscillations in entotic cells show spatiotemporal variations during engulfment, mediated by Orai1 Ca2+ channels in plasma membranes. SEPTIN controlled polarized distribution of Orai1 for local MLCK activation, resulting in MLC phosphorylation and actomyosin contraction, leads to internalization of invasive cells. Ca2+ chelators and SEPTIN, Orai1, and MLCK inhibitors suppress entosis. This study identifies potential targets for treating entosis‐associated tumors, showing that Orai1 is an entotic Ca2+ channel that provides essential Ca2+ signaling and sheds light on the molecular mechanism underlying entosis that involves SEPTIN filaments, Orai1, and MLCK.
Funder
National Research Foundation of Korea
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)