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.

中文翻译：

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前列腺素F2α诱导的前列腺跨膜蛋白，雄激素诱导1介导卵巢癌进展，增加上皮可塑性。

前列腺素（PG）F2α的作用在癌症中的研究很少。我们已经确定PGF2α在卵巢癌中具有新功能，可以刺激前列腺跨膜蛋白雄激素诱导1（PMEPA1）的产生。我们显示这种诱导增加细胞可塑性和增殖，通过PMEPA1增强肿瘤的生长。因此，PMEPA1在卵巢癌细胞中的过表达显着提高了细胞增殖率，而PMEPA1沉默则降低了增殖率。此外，PMEPA1过表达通过减少依赖于SMAD的信号传导来缓冲TGFβ信号传导。PMEPA1过表达的细胞具有上皮形态，与较高的E-钙粘蛋白表达水平相关，而β-catenin核转运受到抑制。虽然，高PMEPA1水平还与上皮到间质转化标记物（例如波形蛋白和ZEB1）相关，从而使细胞能够利用上皮和间质特性，从而获得细胞可塑性和适应性。有趣的是，在小鼠异种移植物中，过度表达PMEPA1的卵巢细胞具有明显的存活和增殖优势，从而具有更高的转移能力，而PMEPA1沉默则具有相反的作用。此外，在一组晚期卵巢癌患者中观察到高PMEPA1表达，与E-钙粘蛋白表达相关。最重要的是，高PMEPA1 mRNA水平与较低的患者生存率相关。有趣的是，在小鼠异种移植物中，过度表达PMEPA1的卵巢细胞具有明显的存活和增殖优势，从而具有更高的转移能力，而PMEPA1沉默则具有相反的作用。此外，在一组晚期卵巢癌患者中观察到高PMEPA1表达，与E-钙粘蛋白表达相关。最重要的是，高PMEPA1 mRNA水平与较低的患者生存率相关。有趣的是，在小鼠异种移植物中，过度表达PMEPA1的卵巢细胞具有明显的存活和增殖优势，从而具有更高的转移能力，而PMEPA1沉默则具有相反的作用。此外，在一组晚期卵巢癌患者中观察到高PMEPA1表达，与E-钙粘蛋白表达相关。最重要的是，高PMEPA1 mRNA水平与较低的患者生存率相关。