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CCCTC-binding factor inhibits breast cancer cell proliferation and metastasis via inactivation of the nuclear
Jie Wu1, Peng-Chang Li1, Jun-Yi Pang2
1Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, 100730, China.
Abstract:
CCCTC-binding factor (CTCF) is an important epigenetic regulator implicated in multiple cellular processes, including growth, proliferation, differentiation, and apoptosis. Although CTCF deletion or mutation has been associated with human breast cancer, the role of CTCF in breast cancer is questionable. We investigated the biological functions of CTCF in breast cancer and the underlying mechanism. The results showed that CTCF expression in human breast cancer cells and tissues was significantly lower than that in normal breast cells and tissues. In addition, CTCF expression correlated significantly with cancer stage (P = 0.043) and pathological differentiation (P = 0.029). Furthermore, CTCF overexpression resulted in the inhibition of proliferation, migration, and invasion, while CTCF knockdown induced these processes in breast cancer cells. Transcriptome analysis and further experimental confirmation in MDA-MD-231 cells revealed that forced overexpression of CTCF might attenuate the DNA-binding ability of nuclear factor-kappaB (NF-κB) p65 subunit and inhibit activation of NF-κB and its target pro-oncogenes (tumor necrosis factor alpha-induced protein 3 [TNFAIP3]) and genes for growth-related proteins (early growth response protein 1 [EGR1] and growth arrest and DNA-damage-inducible alpha [GADD45a]). The present study provides a new insight into the tumor suppressor roles of CTCF in breast cancer development and suggests that the CTCF/NF-κB pathway is a potential target for breast cancer therapy.
Insights
CCCTC-binding factor (CTCF) acts as a tumor suppressor in breast cancer by reducing cell proliferation and invasion. Lower CTCF expression correlates with advanced cancer stages, suggesting its potential as a therapeutic target.
Area of Science:
- Molecular Biology
- Cancer Research
- Epigenetics
Background:
- CCCTC-binding factor (CTCF) is a key epigenetic regulator involved in cellular processes.
- CTCF's role in breast cancer is unclear despite associations with mutations.
Purpose of the Study:
- To investigate the biological functions and mechanisms of CTCF in breast cancer.
- To explore the potential of the CTCF/NF-κB pathway as a therapeutic target.
Main Methods:
- Comparative analysis of CTCF expression in normal and cancerous breast tissues/cells.
- Functional assays (overexpression/knockdown) to assess CTCF's impact on proliferation, migration, and invasion.
- Transcriptome analysis and validation of molecular targets.
Main Results:
- CTCF expression is significantly lower in breast cancer tissues and cells.
- Reduced CTCF correlates with advanced cancer stage and poor differentiation.
- CTCF overexpression inhibits proliferation, migration, and invasion; knockdown promotes these.
- CTCF attenuates NF-κB p65 activity, inhibiting pro-oncogenes like TNFAIP3 and growth factors EGR1 and GADD45a.
Conclusions:
- CTCF functions as a tumor suppressor in breast cancer.
- The CTCF/NF-κB pathway is a promising target for breast cancer therapy.
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