Estrogen/GPR30 Signaling Contributes to the Malignant Potentials of ER-Negative Cervical Adenocarcinoma via Regulation of Claudin-1 Expression
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 cel...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-10-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558618302744 |
| _version_ | 1819194604295028736 |
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| author | Taishi Akimoto Akira Takasawa Kumi Takasawa Tomoyuki Aoyama Masaki Murata Makoto Osanai Tsuyoshi Saito Norimasa Sawada |
| author_facet | Taishi Akimoto Akira Takasawa Kumi Takasawa Tomoyuki Aoyama Masaki Murata Makoto Osanai Tsuyoshi Saito Norimasa Sawada |
| author_sort | Taishi Akimoto |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T01:59:30Z |
| format | Article |
| id | doaj.art-1756d9b80c7941218a0274cba9406495 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 |
| language | English |
| last_indexed | 2024-12-23T01:59:30Z |
| publishDate | 2018-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-1756d9b80c7941218a0274cba94064952022-12-21T18:04:02ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862018-10-01201010831093Estrogen/GPR30 Signaling Contributes to the Malignant Potentials of ER-Negative Cervical Adenocarcinoma via Regulation of Claudin-1 ExpressionTaishi Akimoto0Akira Takasawa1Kumi Takasawa2Tomoyuki Aoyama3Masaki Murata4Makoto Osanai5Tsuyoshi Saito6Norimasa Sawada7Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8556, Japan; Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8556, JapanDepartment of Pathology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8556, Japan; Address all correspondence to: Akira Takasawa, Department of Pathology, Sapporo Medical University School of Medicine, S1 W17, Chuo-ku, Sapporo 060-8556, Japan.Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8556, JapanDepartment of Pathology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8556, JapanDepartment of Pathology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8556, JapanDepartment of Pathology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8556, JapanDepartment of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8556, JapanDepartment of Pathology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8556, JapanCervical 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.http://www.sciencedirect.com/science/article/pii/S1476558618302744 |
| spellingShingle | Taishi Akimoto Akira Takasawa Kumi Takasawa Tomoyuki Aoyama Masaki Murata Makoto Osanai Tsuyoshi Saito Norimasa Sawada 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 |
| title | Estrogen/GPR30 Signaling Contributes to the Malignant Potentials of ER-Negative Cervical Adenocarcinoma via Regulation of Claudin-1 Expression |
| title_full | Estrogen/GPR30 Signaling Contributes to the Malignant Potentials of ER-Negative Cervical Adenocarcinoma via Regulation of Claudin-1 Expression |
| title_fullStr | Estrogen/GPR30 Signaling Contributes to the Malignant Potentials of ER-Negative Cervical Adenocarcinoma via Regulation of Claudin-1 Expression |
| title_full_unstemmed | Estrogen/GPR30 Signaling Contributes to the Malignant Potentials of ER-Negative Cervical Adenocarcinoma via Regulation of Claudin-1 Expression |
| title_short | Estrogen/GPR30 Signaling Contributes to the Malignant Potentials of ER-Negative Cervical Adenocarcinoma via Regulation of Claudin-1 Expression |
| title_sort | estrogen gpr30 signaling contributes to the malignant potentials of er negative cervical adenocarcinoma via regulation of claudin 1 expression |
| url | http://www.sciencedirect.com/science/article/pii/S1476558618302744 |
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