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BMP signaling is a therapeutic target in ovarian cancer.
Fukuda, Tomohiko; Fukuda, Risa; Tanabe, Ryo; Koinuma, Daizo; Koyama, Hiroo; Hashizume, Yoshinobu; Moustakas, Aristidis; Miyazono, Kohei; Heldin, Carl-Henrik.
Afiliación
  • Fukuda T; Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Box 582, Uppsala University, SE-751 23, Uppsala, Sweden. tomohiko.fukuda@imbim.uu.se.
  • Fukuda R; Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Box 582, Uppsala University, SE-751 23, Uppsala, Sweden.
  • Tanabe R; Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1 Bunkyo-ku, Tokyo, 113-8655, Japan.
  • Koinuma D; Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1 Bunkyo-ku, Tokyo, 113-8655, Japan.
  • Koyama H; Drug Discovery Chemistry Platform Unit, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
  • Hashizume Y; RIKEN Program for Drug Discovery and Medical Technology Platforms, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
  • Moustakas A; Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Box 582, Uppsala University, SE-751 23, Uppsala, Sweden.
  • Miyazono K; Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Box 582, Uppsala University, SE-751 23, Uppsala, Sweden. miyazono@m.u-tokyo.ac.jp.
  • Heldin CH; Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1 Bunkyo-ku, Tokyo, 113-8655, Japan. miyazono@m.u-tokyo.ac.jp.
Cell Death Discov ; 6(1): 139, 2020 Dec 05.
Article en En | MEDLINE | ID: mdl-33298901
BMP signaling has been found to have tumor-promoting as well as tumor-suppressing effects in different types of tumors. In this study, we investigated the effects of BMP signaling and of BMP inhibitors on ovarian cancer (OC) cells in vitro and in vivo. High expression of BMP receptor 2 (BMPR2) correlated with poor overall survival of OC patients in the TCGA dataset. Both BMP2 and BMPR2 enhanced OC cell proliferation, whereas BMP receptor kinase inhibitors inhibited OC cell growth in cell culture as well as in a mouse model. BMP2 also augmented sphere formation, migration, and invasion of OC cells, and induced EMT. High BMP2 expression was observed after chemotherapy of OC patients in the GSE109934 dataset. In accordance, carboplatin, used for the treatment of OC patients, increased BMP2 secretion from OC cells, and induced EMT partially via activation of BMP signaling. Our data suggest that BMP signaling has tumor-promoting effects in OC, and that BMP inhibitors might be useful therapeutic agents for OC patients. Considering that carboplatin treatment augmented BMP2 secretion, the possibility to use a combination of BMP inhibitors and carboplatin in the treatment of OC patients, would be worth exploring.

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cell Death Discov Año: 2020 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cell Death Discov Año: 2020 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos