Estrogen/GPR30 Signaling Contributes to the Malignant Potentials of ER-Negative Cervical Adenocarcinoma via Regulation of Claudin-1 Expression

• DOI: 10.1016/j.neo.2018.08.010
• Publication Date: 2018-09-16T02:10:47Z
• Authors: Taishi Akimoto; Akira Takasawa; Kumi Takasawa; Tomoyuki Aoyama; Masaki Murata; Makoto Osanai; Tsuyoshi Saito; Norimasa Sawada
• Keywords: GPER; Claudin; Estrogen receptor beta; Estrogen receptor alpha

Cervical adenocarcinomas are believed to lose estrogen response on the basis of no expression a nuclear receptor such as ERα in clinical pathology. Here, we demonstrated that cervical adenocarcinoma cells respond physiological concentration upregulate claudin-1, cell surface molecule highly expressed adenocarcinomas. Knockout claudin-1 induced apoptosis and significantly inhibited proliferation, migration, invasion tumorigenicity vivo. Importantly, all lines examined membrane-bound type receptor, G protein–coupled 30 (GPR30/GPER1), but not ERα. Estrogen-dependent induction was mediated by GPR30 via ERK and/or Akt signaling. In surgical specimens, there positive correlation between expression. Double high predicts poor prognosis patients with Mechanism-based targeting estrogen/GPR30 signaling may be effective for therapy.