Prostaglandin F2 α-induced Prostate Transmembrane Protein, Androgen Induced 1 mediates ovarian cancer progression increasing epithelial plasticity.

Prostaglandin F2α-induced Prostate Transmembrane Protein, Androgen Induced 1 mediates ovarian cancer progression increasing epithelial plasticity. Neoplasia. 2019 Nov 14;21(11):1073-1084 Authors: Jiménez-Segovia A, Mota A, Rojo-Sebastián A, Barrocal B, Rynne-Vidal A, García-Bermejo ML, Gómez-Bris R, Hawinkels LJAC, Sandoval P, Garcia-Escudero R, López-Cabrera M, Moreno-Bueno G, Fresno M, Stamatakis K Abstract 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. Inter...
Source: Neoplasia - Category: Cancer & Oncology Authors: Tags: Neoplasia Source Type: research