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

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dc.contributor.authorThejer, Bashar M.
dc.contributor.authorAdhikary, Partho P.
dc.contributor.authorKaur, Amandeep
dc.contributor.authorTeakel, Sarah L.
dc.contributor.authorvan Oosterum, Ashleigh
dc.contributor.authorSeth, Ishith
dc.contributor.authorPajic, Marina
dc.contributor.authorHannan, Kate
dc.contributor.authorPavy, Megan
dc.contributor.authorPoh, Perlita
dc.contributor.authorJazayeri, Jalal A.
dc.contributor.authorZaw, Thiri
dc.contributor.authorPascovici, Dana
dc.contributor.authorLudescher, Marina
dc.contributor.authorHannan, Ross
dc.contributor.authorCAHILL, Michael
dc.date.accessioned2023-02-21T23:00:53Z
dc.date.available2023-02-21T23:00:53Z
dc.date.issued2020
dc.date.updated2023-10-22T07:15:58Z
dc.description.abstractBackground 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 suggesting modulation of the Warburg effect. This was associated with increased PI3K/AKT activity, altered cell shape, actin cytoskeleton, motility, and mitochondrial properties. An S57A/Y180F/S181A triple mutant (TM) indicated the involvement of Y180 in PI3K/AKT activation. Mutation of Y180F strongly attenuated subcutaneous xenograft tumor growth in NOD-SCID gamma mice. Elsewhere we demonstrate altered metabolism, mutation incidence, and epigenetic status in these cells. Conclusions Altogether, these results indicate that mutational manipulation of PGRMC1 phosphorylation status exerts broad pleiotropic effects relevant to cancer and other cell biology.
dc.description.sponsorshipThis 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.en_AU
dc.format.mimetypeapplication/pdfen_AU
dc.identifier.issn2661-8850en_AU
dc.identifier.urihttp://hdl.handle.net/1885/285817
dc.language.isoen_AUen_AU
dc.provenanceThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.en_AU
dc.publisherSpringer Nature
dc.relationhttp://purl.org/au-research/grants/arc/CE140100003
dc.relationhttp://purl.org/au-research/grants/arc/DE120102687
dc.rights© 2020 The authors
dc.rights.licenseCreative Commons Attribution licenceen_AU
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_AU
dc.sourceBMC Molecular and Cell Biology
dc.subjectMitochondria
dc.subjectMigration
dc.subjectInvasion
dc.subjectMetabolism
dc.subjectCytochrome P450
dc.subjectMesenchymal amoeboid transition
dc.subjectProteomics
dc.subjectTumor biology
dc.titlePGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth
dc.typeJournal article
dcterms.accessRightsOpen Accessen_AU
local.bibliographicCitation.issue1en_AU
local.contributor.affiliationThejer, Bashar M., Charles Sturt Universityen_AU
local.contributor.affiliationAdhikary, Partho P., Charles Sturt Universityen_AU
local.contributor.affiliationKaur, Amandeep, University of Sydneyen_AU
local.contributor.affiliationTeakel, Sarah L., Charles Sturt Universityen_AU
local.contributor.affiliationvan Oosterum, Ashleigh, Charles Sturt Universityen_AU
local.contributor.affiliationSeth, Ishith, Charles Sturt Universityen_AU
local.contributor.affiliationPajic, Marina, St Vincents Hospital Clinical Schoolen_AU
local.contributor.affiliationHannan, Kate, College of Health and Medicine, ANUen_AU
local.contributor.affiliationPavy, Megan, College of Health and Medicine, ANUen_AU
local.contributor.affiliationPoh, Perlita, College of Health and Medicine, ANUen_AU
local.contributor.affiliationJazayeri, Jalal A., Charles Sturt Universityen_AU
local.contributor.affiliationZaw, Thiri, Macquarie Universityen_AU
local.contributor.affiliationPascovici, Dana, Macquarie Universityen_AU
local.contributor.affiliationLudescher, Marina, University Women's Hospital of Dusseldorfen_AU
local.contributor.affiliationHannan, Ross, College of Health and Medicine, ANUen_AU
local.contributor.affiliationCahill, Michael, College of Health and Medicine, ANUen_AU
local.contributor.authoruidHannan, Kate, u1000189en_AU
local.contributor.authoruidPavy, Megan, u9313370en_AU
local.contributor.authoruidPoh, Perlita, u1032984en_AU
local.contributor.authoruidHannan, Ross, u1000203en_AU
local.contributor.authoruidCahill, Michael, u1075365en_AU
local.description.notesImported from ARIESen_AU
local.identifier.absfor310103 - Cell metabolismen_AU
local.identifier.absfor310105 - Cellular interactions (incl. adhesion, matrix, cell wall)en_AU
local.identifier.absfor321101 - Cancer cell biologyen_AU
local.identifier.absseo200105 - Treatment of human diseases and conditionsen_AU
local.identifier.ariespublicationa383154xPUB11149en_AU
local.identifier.citationvolume21en_AU
local.identifier.doi10.1186/s12860-020-00256-3en_AU
local.identifier.scopusID2-s2.0-85083002791
local.identifier.thomsonIDWOS:000523751700001
local.publisher.urlhttps://bmcmolcellbiol.biomedcentral.com/en_AU
local.type.statusPublished Versionen_AU

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