2. Academic Validation
  3. IGF1R activates FOXP3-β-catenin signaling to promote breast cancer development

IGF1R activates FOXP3-β-catenin signaling to promote breast cancer development

  • Breast Cancer Res Treat. 2025 Mar 7. doi: 10.1007/s10549-025-07663-0.
Lu Li # 1,  Zhiming Zhang # 2,  Na Huang 1,  Jianlan Ren 1,  Yuan Qin 3,  Yangkun Luo 4
Affiliations

Affiliations

  • 1 Radiation Oncology Key Laboratory of Sichuan Province, Department of Radiotherapy, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, Sichuan Cancer Hospital & Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China.
  • 2 Key Laboratory of Environmental and Applied Microbiology, Key Laboratory of Environmental Microbiology of Sichuan Province, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, China.
  • 3 Radiation Oncology Key Laboratory of Sichuan Province, Department of Radiotherapy, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, Sichuan Cancer Hospital & Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China. qinyuan@scszlyy.org.cn.
  • 4 Radiation Oncology Key Laboratory of Sichuan Province, Department of Radiotherapy, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, Sichuan Cancer Hospital & Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China. luoyk@sichuancancer.org.
  • # Contributed equally.
PMID: 40055251 DOI: 10.1007/s10549-025-07663-0
Abstract

Purpose: Forkhead box P3 (FOXP3), a key marker of regulatory T cells (Tregs), is crucial for Treg differentiation and development. Emerging evidence suggests that FOXP3 is also expressed in various tumor cells; however, its role in tumor progression remains controversial. This study aimed to elucidate the impact of FOXP3 on breast Cancer development.

Methods: Breast Cancer cell lines, including HCC1937, HCC1806, Hs 578T, MDA-MB-231, and MCF-7, along with xenograft mouse models, to assess the effects of FOXP3 on cell proliferation and tumor growth. FOXP3 expression in human breast Cancer samples was analyzed using quantitative PCR and immunohistochemistry analyses. Cell proliferation and invasion were evaluated through MTS and transwell assays, respectively. Chromatin immunoprecipitation (ChIP) assays were performed to determine FOXP3 binding to the β-catenin gene promoter.

Results: FOXP3 expression was elevated in advanced breast Cancer and correlates with poor clinical outcomes. FOXP3 directly binds to β-catenin gene promoter - 986 to - 1168 region to facilitate β-catenin transcription, consequently resulting in increased breast Cancer cell proliferation, migration, and invasion in vitro and tumor growth in vivo. Furthermore, IGF1R activated FOXP3-β-catenin signaling to promote breast tumor growth. Moreover, elesclomol, a potent copper ionophore, significantly inhibited FOXP3 expression to suppress breast tumor growth.

Conclusion: This study indicates that FOXP3 plays an oncogenic role in breast Cancer development and suggests that targeting IGF1R-FOXP3-β-catenin signaling may be a putative therapeutic strategy for human breast Cancer treatment.

Keywords

Breast cancer; FOXP3; IGF1R; β-catenin.

Figures
Products