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Published on: January 18, 2017
ZNF133 is a potent suppressor in breast carcinogenesis through dampening L1CAM, a driver for tumor progression
Lifang Li1, Xuefei Wang2, Kai Hu3
1Department of Cancer Cell Biology, Tianjin's Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, PR China. lifangli@bjmu.edu.cn.
Abstract:
Due to the complexity and heterogeneity of breast cancer, the therapeutic effects of breast cancer treatment vary between subtypes. Breast cancer subtypes are classified based on the presence of molecular markers for estrogen or progesterone receptors and human epidermal growth factor 2. Thus, novel, comprehensive, and precise molecular indicators in breast carcinogenesis are urgently needed. Here, we report that ZNF133, a zinc-finger protein, is negatively associated with poor survival and advanced pathological staging of breast carcinomas. Moreover, ZNF133 is a transcription repressor physically associated with the KAP1 complex. It transcriptionally represses a cohort of genes, including L1CAM, that are critically involved in cell proliferation and motility. We also demonstrate that the ZNF133/KAP1 complex inhibits the proliferation and invasion of breast cancer cells in vitro and suppresses breast cancer growth and metastasis in vivo by dampening the transcription of L1CAM. Taken together, the findings of our study confirm the value of ZNF133 and L1CAM levels in the diagnosis and prognosis of breast cancer, contribute to a deeper understanding of the regulation mechanism of ZNF133 for the first time, and provide a new therapeutic strategy and precise intervention target for breast cancer.
Insights
Zinc-finger protein 133 (ZNF133) acts as a tumor suppressor in breast cancer. Its complex inhibits cancer cell proliferation and metastasis, offering a new therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Breast cancer heterogeneity necessitates precise molecular indicators for effective treatment.
- Current classification relies on estrogen/progesterone receptors and human epidermal growth factor 2, but novel markers are needed.
Purpose of the Study:
- To investigate the role of ZNF133 in breast cancer development and progression.
- To elucidate the molecular mechanism by which ZNF133 affects breast cancer cells.
- To identify ZNF133 and L1CAM as potential diagnostic and prognostic markers.
Main Methods:
- Assessed ZNF133 expression in relation to patient survival and tumor stage.
- Identified ZNF133 as a transcription repressor associated with the KAP1 complex.
- Investigated the effect of the ZNF133/KAP1 complex on target genes, including L1CAM.
- Evaluated the impact of ZNF133 on breast cancer cell proliferation, invasion, growth, and metastasis in vitro and in vivo.
Main Results:
- ZNF133 expression is negatively correlated with poor survival and advanced pathological staging in breast cancer.
- ZNF133 transcriptionally represses genes involved in cell proliferation and motility, such as L1CAM.
- The ZNF133/KAP1 complex inhibits breast cancer cell proliferation and invasion in vitro.
- ZNF133 suppresses breast cancer growth and metastasis in vivo by reducing L1CAM transcription.
Conclusions:
- ZNF133 functions as a tumor suppressor in breast cancer.
- ZNF133 and L1CAM levels are valuable for breast cancer diagnosis and prognosis.
- The ZNF133/KAP1 complex presents a novel therapeutic strategy and intervention target for breast cancer.
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