PTGER3 induces ovary tumorigenesis and confers resistance to cisplatin therapy through up-regulation Ras-MAPK/Erk-ETS1-ELK1/CFTR1 axis
Year: 2019
Type: article
Abstract: Background Inflammatory mediator prostaglandin E2–prostaglandin E2 receptor EP3 (PTGER3) signaling is critical for tumor-associated angiogenesis, tumor growth, and chemoresistance. However, the mechanism underlying these effects in ovarian cancer is not known. Methods An association between higher tumoral expression of PTGER3 and shorter patient survival in the ovarian cancer dataset of The Cancer Genome Atlas prompted investigation of the antitumor effects of PTGER3 downmodulation. PTGER3 mRNA and protein levels were higher in cisplatin-resistant ovarian cancer cells than in their cisplatin-sensitive counterparts. Findings Silencing of PTGER3 via siRNA in cancer cells was associated with decreased cell growth and less invasiveness, as well as cell-cycle arrest and increased apoptosis, mediated through the Ras-MAPK/Erk-ETS1-ELK1/CFTR1 axis. Furthermore, sustained PTGER3 silencing with multistage vector and liposomal 2'-F-phosphorodithioate-siRNA–mediated silencing of PTGER3 combined with cisplatin resulted in robust antitumor effects in cisplatin-resistant ovarian cancer models. Interpretation These findings identify PTGER3 as a potential therapeutic target in chemoresistant ovarian cancers expressing high levels of this oncogenic protein. Fund National Institutes of Health/National Cancer Institute, USA.
Source: EBioMedicine
Authors: Cristian Rodriguez-Aguayo, Emine Bayraktar, Cristina Ivan, Burcu Aslan, Junhua Mai, Guangan He, Lingegowda S. Mangala, Dahai Jiang, Archana S. Nagaraja, Bulent Ozpolat, Arturo Chavez-Reyes, Mauro Ferrari, Rahul Mitra, Zahid H. Siddik, Haifa Shen, Xianbin Yang, Anil K. Sood, Gabriel Lopez-Berestein
Institutions: The University of Texas MD Anderson Cancer Center, Gaziantep University, Houston Methodist, Houston Methodist Research Institute, Instituto Politécnico Nacional, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Raptamer Discovery Group (United States)
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,500
Awards: G1570628723, Targeted Development of Platinum Drugs, MD Anderson Gynecologic SPORE for Uterine Cancers, Texas Center for Cancer Nanomedicine, Novel extra cellular RNA-based combinatorial RNA inhibition therapy, (PQD3) The role and therapeutic potential of ZNF304 in Ovarian Cancer, New Reagents for RNA-based Therapeutic Technologies, Clinical Translation of Therapeutic siRNA in Solid Malignancies, UPR/MDACC: Partnership for Excellence in Cancer Research (1 of 2), G4404149503, G6736661663, The University of Texas M. D. Anderson Cancer Center SPORE in Ovarian Cancer, Cancer Center Support Grant, The University of Texas M. D. Anderson Cancer Center SPORE in Melanoma
OpenAlex ID: W2910727582