2. Academic Validation
  3. Rictor orchestrates β-catenin/FOXO balance by maintaining redox homeostasis during development of ovarian cancer

Rictor orchestrates β-catenin/FOXO balance by maintaining redox homeostasis during development of ovarian cancer

  • Oncogene. 2025 Jun;44(23):1820-1832. doi: 10.1038/s41388-025-03351-x.
Xuejiao Zhao # 1 2,  Huiling Lai # 3,  Guannan Li # 1 2,  Yu Qin 1 2,  Ruqi Chen 1 2,  Marilyne Labrie 4,  Jayne M Stommel 5,  Gordon B Mills 5 6,  Ding Ma 7 8,  Qinglei Gao 9 10,  Yong Fang 11 12
Affiliations

Affiliations

  • 1 National Clinical Research Center for Obstetrics and Gynaecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Department of Gynaecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 3 Department of Gynecology, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
  • 4 Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.
  • 5 Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • 6 Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR, USA.
  • 7 National Clinical Research Center for Obstetrics and Gynaecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. dma@tjh.tjmu.edu.cn.
  • 8 Department of Gynaecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. dma@tjh.tjmu.edu.cn.
  • 9 National Clinical Research Center for Obstetrics and Gynaecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. qlgao@tjh.tjmu.edu.cn.
  • 10 Department of Gynaecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. qlgao@tjh.tjmu.edu.cn.
  • 11 National Clinical Research Center for Obstetrics and Gynaecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. tongjify@163.com.
  • 12 Department of Gynaecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. tongjify@163.com.
  • # Contributed equally.
PMID: 40133477 DOI: 10.1038/s41388-025-03351-x
Abstract

Rictor/mTORC2 has been demonstrated to have important roles in Cancer development and progression in a number of solid and hematologic malignancies. However, little is known about the role of Rictor/mTORC2 in ovarian Cancer pathophysiology. Herein, using conditional Rictor knockout mice, we were able to demonstrate that Rictor deletion disrupted glutathione metabolism through Akt/Nrf2 signaling pathway and induced intracellular oxidative stress during the malignant transformation of Kras/Pten-mutant ovarian surface epithelial cells. Elevated Reactive Oxygen Species and activated FOXO3a in Rictor-deleted cells strikingly shifts the functional interaction of β-catenin from TCF to FOXO3a, which strongly inhibits classical Wnt/β-catenin signaling. Our findings emphasize a pivotal role for Rictor in orchestrating crosstalk between the PI3K/Akt and Wnt/β-catenin signaling in the development of ovarian Cancer. Illustration of Rictor/mTORC2 in promoting tumor onset by regulating glutathione metabolism and mediating oncogenic signaling.

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