2. Academic Validation
  3. Therapeutic targeting of STING-IL6/STAT3 axis to inhibit osteoclastic niche formation and breast cancer bone metastasis

Therapeutic targeting of STING-IL6/STAT3 axis to inhibit osteoclastic niche formation and breast cancer bone metastasis

  • Cell Death Discov. 2025 Oct 24;11(1):483. doi: 10.1038/s41420-025-02776-3.
Chen Zhao # 1,  Pengcheng Liu # 2,  Keyu Kong 1,  Xuzhuo Chen 3,  Junxiang Wu 4,  Wen Wu 5,  Xiaoqing Wang 6,  Lei Wang 7
Affiliations

Affiliations

  • 1 Department of Orthopedics, Shanghai Key Laboratory of Orthopedics Implant, The Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3 Department of Oral Surgery, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 4 Department of Orthopedics, Shanghai Key Laboratory of Orthopedics Implant, The Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. wujunxiang9503@163.com.
  • 5 Department of Orthopedics, Shanghai Key Laboratory of Orthopedics Implant, The Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 13761003720@163.com.
  • 6 Department of Orthopedics, Shanghai Key Laboratory of Orthopedics Implant, The Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. osteoclast2006@sjtu.edu.cn.
  • 7 Department of Orthopedics, Shanghai Key Laboratory of Orthopedics Implant, The Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. wanglsjtu@163.com.
  • # Contributed equally.
PMID: 41136375 DOI: 10.1038/s41420-025-02776-3
Abstract

Despite numerous studies on tumor bone metastasis, little emphasis has been placed on the role of the formation of the osteoclastic premetastatic niche (OPN), and related genetic intervention targets are relatively scarce. Our data confirm the promoting effect of OPN formation on bone metastasis and demonstrate the existence of a vicious cycle between osteoclast differentiation and breast tumor cell proliferation through in vitro cell experiments. Moreover, we show that regulating Stimulator of Interferon Genes (STING) can break this cycle. However, both in vivo and in vitro experiments further indicate that STING intervention in OPN formation and breast tumor bone metastasis depends on IL6/STAT3, with a significant discount in the presence of IL-6 activation. In summary, these data not only highlight the important role of OPN but also emphasize STING-IL6/STAT3 as a crucial intervention target.

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