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.

Oncotarget
|December 8, 2017
PubMed

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.

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.1K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
10.1K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.9K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
8.7K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
8.2K
Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
6.7K