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Updated: Aug 16, 2025

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
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Zinc-finger protein CXXC5 promotes breast carcinogenesis by regulating the TSC1/mTOR signaling pathway

Wenjuan Wang1, Zhaohan Zhang1, Minghui Zhao1

  • 1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.

The Journal of Biological Chemistry
|December 20, 2022
PubMed

Insights

CXXC5 protein interacts with CRL4B and NuRD complexes, suppressing TSC1 and promoting tumor growth. This CXXC5-mediated pathway activates mTOR signaling, reduces cell death, and induces immune suppression, contributing to cancer development.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • CXXC5, a zinc-finger protein, is implicated in various pathological processes, but its specific pathophysiological role remains unclear.
  • Understanding the molecular mechanisms underlying CXXC5 function is crucial for developing targeted cancer therapies.

Purpose of the Study:

  • To elucidate the pathophysiological function of CXXC5 and its molecular interactions.
  • To investigate the role of the CXXC5-CRL4B-NuRD complex in gene regulation and tumor development, particularly in breast cancer.

Main Methods:

  • Chromatin immunoprecipitation sequencing (ChIP-seq) to identify transcriptional targets of the CXXC5-CRL4B-NuRD complex.
  • In vitro and in vivo studies to assess the impact of CXXC5 on tumor cell proliferation and breast cancer growth.
  • Analysis of gene expression in breast cancer tissues and correlation with clinical parameters.

Main Results:

  • CXXC5 interacts with CRL4B and NuRD complexes, regulating transcriptional repression of genes including TSC1.
  • The CXXC5-CRL4B-NuRD complex promotes tumor cell proliferation and breast cancer growth by suppressing TSC1, activating mTOR signaling, reducing autophagic cell death, and inducing PD-L1-mediated immune suppression.
  • Increased expression of CXXC5, CUL4B, and MTA1, and decreased TSC1 expression correlate with breast cancer progression.
  • High CXXC5 expression is linked to higher malignancy grade and poorer patient survival.

Conclusions:

  • CXXC5 plays a significant role in tumor development through TSC1 suppression, leading to mTOR pathway activation, reduced autophagy, and immune evasion.
  • The CXXC5-CRL4B-NuRD complex represents a potential therapeutic target for breast cancer and other malignancies.
  • Further research into CXXC5 regulation by vitamins may offer novel therapeutic strategies.
Keywords:
PD-L1-mediated immune suppressionmTOR signaling pathwaytranscription factor CXXC5transcription repressionvitamin

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