Journal article

PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

Bashar M Thejer, Partho P Adhikary, Amandeep Kaur, Sarah L Teakel, Ashleigh Van Oosterum, Ishith Seth, Marina Pajic, Katherine M Hannan, Megan Pavy, Perlita Poh, Jalal A Jazayeri, Thiri Zaw, Dana Pascovici, Marina Ludescher, Michael Pawlak, Juan C Cassano, Lynne Turnbull, Mitra Jazayeri, Alexander C James, Craig P Coorey Show all



BACKGROUND: Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, where it is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarily preceded deuterostome gastrulation and tissue differentiation mechanisms. RESULTS: We demonstrate that manipulating PGRMC1 phosphorylation status in MIA PaCa-2 (MP) cells imposes broad pleiotropic effects. Relative to parental cells over-expressing hemagglutinin-tagged wild-type (WT) PGRMC1-HA, cells expressing a PGRMC1-HA-S57A/S181A double mutant (DM) exhibited reduced levels of proteins involved in energy metabolism and mitochondrial function, and altered glucose metabolism sugg..

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Awarded by Australian Research Council

Awarded by Ramaciotti Foundation

Funding Acknowledgements

This work has received no direct Australian competitive grant support since M.A.C.'s relocation to the country in 2008. The present results have been compiled largely due to the generosity of collaborating authors, and by the PhD stipends of B.M.T. and P.P.A. Research was primarily supported by Charles Sturt University internal funds to M.A.C and J.A.J, and by collaborating labs. Open access publication fees were jointly supported by CSU's Faculty of Science, School of Biomedical Sciences, and Research Office. B.M.T. was supported by a PhD scholarship from the Ministry of Higher Education and Research, through the University of Wasit, Iraq. A.K. acknowledges the University of Sydney for a World Scholars Scholarship. E.M.G. acknowledges partial support of Australian Research Council award CE140100003. E.J.N. acknowledges the support of the Australian Research Council (DE120102687) and the Ramaciotti Foundation (ES2012/0051). T.L.R is supported by a Cancer Institute New South Wales Future Research Leader Fellowship. M.P. is supported by a NHMRC RD Wright Biomedical Career Development Fellowship and the Cancer Institute NSW Career Development Fellowship. The funding bodies played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.