Prostaglandin F2α-induced Prostate Transmembrane Protein, Androgen Induced 1 mediates ovarian cancer progression increasing epithelial plasticity
The role of prostaglandin (PG) F2α has been scarcely studied in cancer. We have identified a new function for PGF2α in ovarian cancer, stimulating the production of Prostate Transmembrane Protein, Androgen Induced 1 (PMEPA1). We show that this induction increases cell plasticity and proliferation, e...
Main Authors: | , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Elsevier
2019-11-01
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Series: | Neoplasia: An International Journal for Oncology Research |
Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558619302878 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alba Jiménez-Segovia Alba Mota Alejandro Rojo-Sebastián Beatriz Barrocal Angela Rynne-Vidal María-Laura García-Bermejo Raquel Gómez-Bris Lukas J.A.C. Hawinkels Pilar Sandoval Ramon Garcia-Escudero Manuel López-Cabrera Gema Moreno-Bueno Manuel Fresno Konstantinos Stamatakis |
spellingShingle |
Alba Jiménez-Segovia Alba Mota Alejandro Rojo-Sebastián Beatriz Barrocal Angela Rynne-Vidal María-Laura García-Bermejo Raquel Gómez-Bris Lukas J.A.C. Hawinkels Pilar Sandoval Ramon Garcia-Escudero Manuel López-Cabrera Gema Moreno-Bueno Manuel Fresno Konstantinos Stamatakis Prostaglandin F2α-induced Prostate Transmembrane Protein, Androgen Induced 1 mediates ovarian cancer progression increasing epithelial plasticity Neoplasia: An International Journal for Oncology Research |
author_facet |
Alba Jiménez-Segovia Alba Mota Alejandro Rojo-Sebastián Beatriz Barrocal Angela Rynne-Vidal María-Laura García-Bermejo Raquel Gómez-Bris Lukas J.A.C. Hawinkels Pilar Sandoval Ramon Garcia-Escudero Manuel López-Cabrera Gema Moreno-Bueno Manuel Fresno Konstantinos Stamatakis |
author_sort |
Alba Jiménez-Segovia |
title |
Prostaglandin F2α-induced Prostate Transmembrane Protein, Androgen Induced 1 mediates ovarian cancer progression increasing epithelial plasticity |
title_short |
Prostaglandin F2α-induced Prostate Transmembrane Protein, Androgen Induced 1 mediates ovarian cancer progression increasing epithelial plasticity |
title_full |
Prostaglandin F2α-induced Prostate Transmembrane Protein, Androgen Induced 1 mediates ovarian cancer progression increasing epithelial plasticity |
title_fullStr |
Prostaglandin F2α-induced Prostate Transmembrane Protein, Androgen Induced 1 mediates ovarian cancer progression increasing epithelial plasticity |
title_full_unstemmed |
Prostaglandin F2α-induced Prostate Transmembrane Protein, Androgen Induced 1 mediates ovarian cancer progression increasing epithelial plasticity |
title_sort |
prostaglandin f2α-induced prostate transmembrane protein, androgen induced 1 mediates ovarian cancer progression increasing epithelial plasticity |
publisher |
Elsevier |
series |
Neoplasia: An International Journal for Oncology Research |
issn |
1476-5586 |
publishDate |
2019-11-01 |
description |
The role of prostaglandin (PG) F2α has been scarcely studied in cancer. We have identified a new function for PGF2α 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 TGFβ signaling, via reduction of SMAD-dependent signaling. PMEPA1 overexpressing cells acquired an epithelial morphology, associated with higher E-cadherin expression levels while β-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 E-cadherin expression. Most importantly, high PMEPA1 mRNA levels were associated with lower patient survival. |
url |
http://www.sciencedirect.com/science/article/pii/S1476558619302878 |
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doaj-ab84a5ae9764410dbac8933e3cf2d65a2020-11-25T01:35:07ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862019-11-01211110731084Prostaglandin F2α-induced Prostate Transmembrane Protein, Androgen Induced 1 mediates ovarian cancer progression increasing epithelial plasticityAlba Jiménez-Segovia0Alba Mota1Alejandro Rojo-Sebastián2Beatriz Barrocal3Angela Rynne-Vidal4María-Laura García-Bermejo5Raquel Gómez-Bris6Lukas J.A.C. Hawinkels7Pilar Sandoval8Ramon Garcia-Escudero9Manuel López-Cabrera10Gema Moreno-Bueno11Manuel Fresno12Konstantinos Stamatakis13Centro de Biología Molecular “Severo Ochoa” (Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), c/ Nicolás Cabrera, 1, Campus Cantoblanco, Universidad Autónoma de Madrid, Madrid 28049, SpainDepartamento de Bioquímica, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas ‘Alberto Sols’ (CSIC-UAM), IdiPaz, Madrid, Spain; MD Anderson Cancer Center Madrid & Fundación MD Anderson Internacional, Madrid, SpainMD Anderson Cancer Center Madrid & Fundación MD Anderson Internacional, Madrid, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), SpainCentro de Biología Molecular “Severo Ochoa” (Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), c/ Nicolás Cabrera, 1, Campus Cantoblanco, Universidad Autónoma de Madrid, Madrid 28049, SpainCentro de Biología Molecular “Severo Ochoa” (Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), c/ Nicolás Cabrera, 1, Campus Cantoblanco, Universidad Autónoma de Madrid, Madrid 28049, SpainBiomarkers and Therapeutic Targets Lab, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, SpainCentro de Biología Molecular “Severo Ochoa” (Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), c/ Nicolás Cabrera, 1, Campus Cantoblanco, Universidad Autónoma de Madrid, Madrid 28049, SpainDepartment of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, the NetherlandsCentro de Biología Molecular “Severo Ochoa” (Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), c/ Nicolás Cabrera, 1, Campus Cantoblanco, Universidad Autónoma de Madrid, Madrid 28049, SpainCentro de Investigación Biomédica en Red de Cáncer (CIBERONC), Spain; Molecular Oncology Unit, CIEMAT, Madrid, Spain; Biomedical Research Institute I+12, University Hospital 12 de Octubre, Madrid 28041, SpainCentro de Biología Molecular “Severo Ochoa” (Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), c/ Nicolás Cabrera, 1, Campus Cantoblanco, Universidad Autónoma de Madrid, Madrid 28049, SpainDepartamento de Bioquímica, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas ‘Alberto Sols’ (CSIC-UAM), IdiPaz, Madrid, Spain; MD Anderson Cancer Center Madrid & Fundación MD Anderson Internacional, Madrid, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), SpainCentro de Biología Molecular “Severo Ochoa” (Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), c/ Nicolás Cabrera, 1, Campus Cantoblanco, Universidad Autónoma de Madrid, Madrid 28049, Spain; Instituto de Investigación Sanitaria Hospital Universitario de la Princesa (IIS-P), Madrid, Spain; Corresponding authors at: Centro de Biología Molecular “Severo Ochoa” (Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), c/ Nicolás Cabrera, 1, Campus Cantoblanco, Universidad Autónoma de Madrid, Madrid 28049, Spain.Centro de Biología Molecular “Severo Ochoa” (Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), c/ Nicolás Cabrera, 1, Campus Cantoblanco, Universidad Autónoma de Madrid, Madrid 28049, Spain; Instituto de Investigación Sanitaria Hospital Universitario de la Princesa (IIS-P), Madrid, Spain; Corresponding authors at: Centro de Biología Molecular “Severo Ochoa” (Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), c/ Nicolás Cabrera, 1, Campus Cantoblanco, Universidad Autónoma de Madrid, Madrid 28049, Spain.The role of prostaglandin (PG) F2α has been scarcely studied in cancer. We have identified a new function for PGF2α 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 TGFβ signaling, via reduction of SMAD-dependent signaling. PMEPA1 overexpressing cells acquired an epithelial morphology, associated with higher E-cadherin expression levels while β-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 E-cadherin expression. Most importantly, high PMEPA1 mRNA levels were associated with lower patient survival.http://www.sciencedirect.com/science/article/pii/S1476558619302878 |