PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth
department or school: Pharmaceutical Sciences, Faculty of
department or school: Non UBC
data provider: DSpace
identifier citation: BMC Molecular and Cell Biology. 2020 Apr 03;21(1):24
rights copyright: The Author(s)
creator: Thejer, Bashar M
creator: Adhikary, Partho P
creator: Kaur, Amandeep
creator: Teakel, Sarah L
creator: Van Oosterum, Ashleigh
creator: Seth, Ishith
creator: Pajic, Marina
creator: Hannan, Katherine M
creator: Pavy, Megan
creator: Poh, Perlita
creator: Jazayeri, Jalal A
creator: Zaw, Thiri
creator: Pascovici, Dana
creator: Ludescher, Marina
creator: Pawlak, Michael
creator: Cassano, Juan C
creator: Turnbull, Lynne
creator: Jazayeri, Mitra
creator: James, Alexander C
creator: Coorey, Craig P
creator: Roberts, Tara L
creator: Kinder, Simon J
creator: Hannan, Ross D
creator: Patrick, Ellis
creator: Molloy, Mark P
creator: New, Elizabeth J
creator: Fehm, Tanja N
creator: Neubauer, Hans
creator: Goldys, Ewa M
creator: Weston, Leslie A
creator: Cahill, Michael A
issued: 2020-04-03T20:13:01Z
issued: 2020-04-03
description: 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 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.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/73900
note: RESEARCH ARTICLE Open AccessPGRMC1 phosphorylation affects cell shape,motility, glycolysis, mitochondrial form andfunction, and tumor growthBashar M. Thejer1,2†, Partho P. Adhikary1,3†, Amandeep Kaur4,5, Sarah L. Teakel1, Ashleigh Van Oosterum6,Ishith Seth1, Marina Pajic7,8, Katherine M. Hannan9,10, Megan Pavy10, Perlita Poh10, Jalal A. Jazayeri1, Thiri Zaw11,Dana Pascovici11, Marina Ludescher12, Michael Pawlak13, Juan C. Cassano14, Lynne Turnbull15,16, Mitra Jazayeri17,Alexander C. James18,19,20, Craig P. Coorey18,21, Tara L. Roberts18,19,20,21, Simon J. Kinder22, Ross D. Hannan9,10,23,24,25,Ellis Patrick26, Mark P. Molloy11,27, Elizabeth J. New4, Tanja N. Fehm12, Hans Neubauer12, Ewa M. Goldys28,29,Leslie A. Weston30,31 and Michael A. Cahill1,10*AbstractBackground: Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, whereit is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarilypreceded deuterostome gastrulation and tissue differentiation mechanisms.Results: We demonstrate that manipulating PGRMC1 phosphorylation status in MIA PaCa-2 (MP) cells imposesbroad 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 involvedin energy metabolism and mitochondrial function, and altered glucose metabolism suggesting modulation of theWarburg 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 gammamice. Elsewhere we demonstrate altered metabolism, mutation incidence, and epigenetic status in these cells.Conclusions: Altogether, these results indicate that mutational manipu…
has type: Article
is shown at: 10.14288/1.0389730
language: eng
peer review status: Reviewed
provider: Vancouver : University of British Columbia Library
publisher: BioMed Central
publisher DOI: 10.1186/s12860-020-00256-3
rights: Attribution 4.0 International (CC BY 4.0)
rights URI: http://creativecommons.org/licenses/by/4.0/
scholar level: Faculty
subject: Mitochondria
subject: Migration
subject: Invasion
subject: Metabolism
subject: Cytochrome P450
subject: Mesenchymal amoeboid transition
subject: Proteomics
subject: Tumor biology
type: Text
identifier URI: http://hdl.handle.net/2429/73900