Epithelial-mesenchymal transition, IP3 receptors and ER-PM junctions: translocation of Ca2+ signalling complexes and regulation of migration.

Autor:	Okeke E; Department of Cellular and Molecular Physiology, University of Liverpool, Crown Street, Liverpool L69 3BX, U.K., Parker T; Department of Cellular and Molecular Physiology, University of Liverpool, Crown Street, Liverpool L69 3BX, U.K., Dingsdale H; Department of Cellular and Molecular Physiology, University of Liverpool, Crown Street, Liverpool L69 3BX, U.K., Concannon M; Department of Cellular and Molecular Physiology, University of Liverpool, Crown Street, Liverpool L69 3BX, U.K., Awais M; NIHR Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Crown Street, Liverpool L69 3BX, U.K., Voronina S; Department of Cellular and Molecular Physiology, University of Liverpool, Crown Street, Liverpool L69 3BX, U.K., Molgó J; CEA, Institut de Biologie et Technologies de Saclay (iBiTec-S), Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), bâtiment 152, 91191 Gif-sur-Yvette Cedex, France Institut des Neurosciences Paris-Saclay, UMR 9197, CNRS/Université Paris-Sud, CNRS, 91190-Gif sur Yvette Cedex, France., Begg M; Respiratory Therapy Area Unit, Medicines Research Centre, GlaxoSmithKline, Stevenage SG1 2NY, England, U.K., Metcalf D; Biotechnology Group, National Physical Laboratory, Hampton Road, Teddington TW11 0LW, U.K., Knight AE; Biotechnology Group, National Physical Laboratory, Hampton Road, Teddington TW11 0LW, U.K., Sutton R; NIHR Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Crown Street, Liverpool L69 3BX, U.K., Haynes L; Department of Cellular and Molecular Physiology, University of Liverpool, Crown Street, Liverpool L69 3BX, U.K., Tepikin AV; Department of Cellular and Molecular Physiology, University of Liverpool, Crown Street, Liverpool L69 3BX, U.K. a.tepikin@liv.ac.uk.
Jazyk:	angličtina
Zdroj:	The Biochemical journal [Biochem J] 2016 Mar 15; Vol. 473 (6), pp. 757-67. Date of Electronic Publication: 2016 Jan 12.
DOI:	10.1042/BJ20150364
Abstrakt:	Disconnection of a cell from its epithelial neighbours and the formation of a mesenchymal phenotype are associated with profound changes in the distribution of cellular components and the formation of new cellular polarity. We observed a dramatic redistribution of inositol trisphosphate receptors (IP3Rs) and stromal interaction molecule 1 (STIM1)-competent endoplasmic reticulum-plasma membrane junctions (ER-PM junctions) when pancreatic ductal adenocarcinoma (PDAC) cells disconnect from their neighbours and undergo individual migration. In cellular monolayers IP3Rs are juxtaposed with tight junctions. When individual cells migrate away from their neighbours IP3Rs preferentially accumulate at the leading edge where they surround focal adhesions. Uncaging of inositol trisphosphate (IP3) resulted in prominent accumulation of paxillin in focal adhesions, highlighting important functional implications of the observed novel structural relationships. ER-PM junctions and STIM1 proteins also migrate to the leading edge and position closely behind the IP3Rs, creating a stratified distribution of Ca(2+) signalling complexes in this region. Importantly, migration of PDAC cells was strongly suppressed by selective inhibition of IP3Rs and store-operated Ca(2+) entry (SOCE), indicating that these mechanisms are functionally required for migration. (© 2016 Authors.)
Databáze:	MEDLINE
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