2. Academic Validation
  3. Therapeutic targeting of interleukin-17C signaling in carcinogenesis of endometriosis

Therapeutic targeting of interleukin-17C signaling in carcinogenesis of endometriosis

  • Cell Rep Med. 2025 Dec 16;6(12):102464. doi: 10.1016/j.xcrm.2025.102464.
Bo Yao 1,  Ruxin Zheng 2,  Yabing Yang 3,  Zhan Zhao 4,  Gendie E Lash 5,  Bihui Guo 6,  Jinghua Pan 4,  Hanlin Shuai 7,  Hong Zhou 8,  Minghua Wang 9,  Ping Li 10
Affiliations

Affiliations

  • 1 Department of Pathology, Jinan University School of Medicine, Guangzhou 510632, China.
  • 2 Department of Pathology, Jinan University School of Medicine, Guangzhou 510632, China; Department of Pathology, Longgang District People's Hospital, The Second Affiliated Hospital of The Chinese University of Hong Kong, Shenzhen 518172, China.
  • 3 Department of Systems Biomedical Sciences, School of Medicine, Jinan University, Guangzhou 510632, China.
  • 4 Department of General Surgery, First Affiliated Hospital of Jinan University, Guangzhou 510632, China.
  • 5 Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China.
  • 6 Department of Obstetrics and Gynecology, Huizhou Second Maternal and Child Health Hospital, Huizhou, China.
  • 7 Center of Reproductive Medicine, First Affiliated Hospital of Jinan University, Guangzhou 510632, China.
  • 8 Center of Reproductive Medicine, First Affiliated Hospital of Jinan University, Guangzhou 510632, China. Electronic address: [email protected].
  • 9 Department of Pathology, Longgang District People's Hospital, The Second Affiliated Hospital of The Chinese University of Hong Kong, Shenzhen 518172, China. Electronic address: [email protected].
  • 10 Department of Pathology, Jinan University School of Medicine, Guangzhou 510632, China. Electronic address: [email protected].
PMID: 41270735 DOI: 10.1016/j.xcrm.2025.102464
Abstract

Endometriosis-associated ovarian carcinoma (EAOC) predominantly arises from the malignant transformation of endometriomas, yet the mechanism is incompletely defined. Spatial transcriptomic analysis of human specimens of normal endometrium, endometriomas, and EAOC identified interleukin-17C (IL-17C) signaling activation, with higher IL-17 Receptor E (IL-17RE) expression in EAOC. Additionally, the IL-17C concentration was significantly increased in the peritoneal fluid of women with ovarian Cancer. Using an endometriosis mouse model overexpressing IL-17RE, IL-17C levels were elevated in the peritoneal fluid. Furthermore, IL-17C knockout reduced the peritoneal fluid IL-17C concentration and inhibited ectopic lesion growth in endometriosis mice. In addition, the role of IL-17C signaling in promoting endometriosis carcinogenesis was investigated by blocking and modulating the IL-17C/IL-17RE pathway in human endometriotic epithelial cells, endometrial organoids, and ovarian endometriosis mice. These data identified IL-17C signaling as a driver of endometriosis carcinogenesis and propose IL-17C/IL-17RE as promising therapeutic targets, particularly for EAOC cases characterized by high IL-17C expression.

Keywords

IL-17C; IL-17RE; carcinogenesis; endometriosis; endometriosis-associated ovarian carcinoma.

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