The tumor suppressor SALL2 opposes chemotherapeutic resistance in breast cancer
Chemotherapy continues to be the primary treatment for certain types of breast cancer. However, despite an initial positive response to chemotherapeutic agents, the development of resistance is inevitable. The exact molecular mechanisms underlying this phenomenon remain unclear. In this research, a significant downregulation of SALL2 expression was observed in chemo-resistant breast cancer, which was attributed to promoter methylation. Decreased SALL2 expression correlated significantly with poorer relapse-free survival in chemotherapy-treated patients with breast cancer. Functionally, SALL2 silencing induced a stem cell-like phenotype in breast cancer cells, fostering resistance to cisplatin both in vitro and in vivo. This resistance was mediated, at least in part, through the transcriptional regulation of BTG2, a negative regulator of stemness, achieved by direct binding to its promoter regions. These findings underscore the critical role of SALL2 in modulating cisplatin response and propose SALL2 as a potential prognostic biomarker for chemotherapy response in breast cancer.
Authors
- Chengming Zhu (ORCID: https://orcid.org/0000-0001-5976-6172)
- Qingqing Zhu (ORCID: https://orcid.org/0000-0001-5344-7648)
- Yuhao Zhang (ORCID: https://orcid.org/0000-0002-6801-9010)
- Yun Wang (ORCID: https://orcid.org/0000-0003-0408-6879)
- Wanhui Xu
- Chenxin Li (ORCID: https://orcid.org/0000-0002-6276-7712)
- Qiji Li (ORCID: https://orcid.org/0000-0001-7949-299X)
- Zihan Zheng (ORCID: https://orcid.org/0000-0003-1486-9586)
- Meng Wang (ORCID: https://orcid.org/0000-0002-3094-7735)
- Yongfeng Yang (ORCID: https://orcid.org/0009-0001-9266-0916)
- Qin Tian
- Liping Ye (ORCID: https://orcid.org/0000-0002-2263-0631)
- Rui Wang (ORCID: https://orcid.org/0009-0005-8109-7688)
Institutions
- Sun Yat-sen University (CN)
- Wuhan University (CN)
- The Seventh Affiliated Hospital of Sun Yat-sen University (CN)
- Zhongnan Hospital of Wuhan University (CN)
Publication Details
- Journal
- Molecular and Cellular Biochemistry
- Published
- 2024-11-22
- DOI
- https://doi.org/10.1007/s11010-024-05155-1
- Citations
- 1
- Primary Topic
- Renal and related cancers
- Type
- article
- Field-Weighted Citation Impact
- 0.23
Funders
- National Natural Science Foundation of China
- Fundamental Research Funds for the Central Universities
- Shenzhen Science and Technology Innovation Program
- Basic and Applied Basic Research Foundation of Guangdong Province