Prostaglandin F 2α-induced prostate transmembrane protein, androgen induced 1 mediates ovarian cancer progression increasing epithelial plasticity
Author
Jiménez-Segovia, Alba; Mota, Alba; Rojo-Sebastián, Alejandro; Barrocal, Beatriz; Rynne-Vidal, Ángela; García-Bermejo, Mara-Laura; Gómez-Bris, Raquel; Hawinkels, Lukas J.A.C.; Sandoval, Pilar; García-Escudero, Ramón; López-Cabrera, Manuel; Moreno Bueno, Gema; Fresno Escudero, Manuel; Stamatakis Andriani, Konstantinos; Centro de Biología Molecular Severo Ochoa (CBMSO); Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM); Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-IP)Entity
UAM. Departamento de BioquímicaPublisher
Elsevier Inc. on behalf of Neoplasia PressDate
2019Citation
10.1016/j.neo.2019.10.001
Neoplasia 21.11 (2019): 1073-1084
ISSN
1522-8002 (print); 1476-5586 (online)DOI
10.1016/j.neo.2019.10.001Funded by
This work was supported by grants from Ministerio de Ciencia e Innovación (SAF201342850R and SAF201675988R) Comunidad de Madrid (S2017/BMD3671. INFLAMUNECM), Fondo de Investigaciones Sanitarias (BIOIMID) to M.F. and grants from the AECC (Grupos Estables de Investigacion 2011AECC GCB 110333 REVE) and the Instituto de Salud Carlos III (ISCIII: PI16/00134 and CIBEONC: CB16/12/00295) to G.M.B. K.S. was recipient of a Spanish Association Against Cancer oncology investigator grant (AECC AIO). A.J.S. and AM were recipients of FPU predoctoral fellowships from the Spanish Ministry of Education, Culture and Sports (FPU20122084 and 5338, respectively).Project
Gobierno de España. SAF201342850R; Gobierno de España. SAF201675988R; Gobierno de España. PI16/00134; Comunidad de Madrid. S2017/BMD3671/INFLAMUNEEditor's Version
https://doi.org/10.1016/j.neo.2019.10.001Subjects
Prostaglandin; Cancer; Ovarian cancer; E-cadherin expression; High PMEPA1 mRNA levels; MedicinaRights
© 2019 The AuthorsEsta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional.
Abstract
The role of prostaglandin (PG) F2a has been scarcely studied in cancer. We have identified a new function for PGF2a in ovarian
cancer, stimulating the production of Prostate Transmembrane Protein, Androgen Induced 1 (PMEPA1). We show that this induction
increases cell plasticity and proliferation, enhancing tumor growth through PMEPA1. Thus, PMEPA1 overexpression in ovarian
carcinoma cells, significantly increased cell proliferation rates, whereas PMEPA1 silencing decreased proliferation. In addition,
PMEPA1 overexpression buffered TGF signaling, via reduction of SMADdependent signaling. PMEPA1 overexpressing cells
acquired an epithelial morphology, associated with higher Ecadherin expression levels while catenin nuclear translocation was inhibited.
Notwithstanding, high PMEPA1 levels also correlated with epithelial to mesenchymal transition markers, such as vimentin and
ZEB1, allowing the cells to take advantage of both epithelial and mesenchymal characteristics, gaining in cell plasticity and adaptability.
Interestingly, in mouse xenografts, PMEPA1 overexpressing ovarian cells had a clear survival and proliferative advantage,
resulting in higher metastatic capacity, while PMEPA1 silencing had the opposite effect. Furthermore, high PMEPA1 expression
in a cohort of advanced ovarian cancer patients was observed, correlating with Ecadherin expression. Most importantly, high
PMEPA1 mRNA levels were associated with lower patient survival
Files in this item
Google Scholar:Jiménez-Segovia, Alba
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Mota, Alba
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Rojo-Sebastián, Alejandro
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Barrocal, Beatriz
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Rynne-Vidal, Ángela
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García-Bermejo, Mara-Laura
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Gómez-Bris, Raquel
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Hawinkels, Lukas J.A.C.
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Sandoval, Pilar
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García-Escudero, Ramón
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López-Cabrera, Manuel
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Moreno Bueno, Gema
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Fresno Escudero, Manuel
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Stamatakis Andriani, Konstantinos
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Centro de Biología Molecular Severo Ochoa (CBMSO)
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Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)
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Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-IP)
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