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

Neoplasia : an International Journal for Oncology Research
Taishi AkimotoNorimasa Sawada

Abstract

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

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Citations

Sep 26, 2020·Frontiers in Endocrinology·Christian David Hernández-SilvaAna Laura Pereira-Suárez
Oct 23, 2020·Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association·Hande Mefkure OzkayaPinar Kadioglu
Jun 6, 2021·Biochemical and Biophysical Research Communications·Kumi TakasawaMakoto Osanai
Aug 7, 2021·Frontiers in Oncology·Jian Li
Aug 14, 2021·Oncology Letters·Jian Li

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Methods Mentioned

BETA
Transfection
FACS
PCR
Xenograft
surgical resections
confocal microscopy

Software Mentioned

CRISPR direct
EZR

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