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CDK2-activated TRIM32 phosphorylation and nuclear translocation promotes radioresistance in triple-negative breast

Jianming Tang1, Jing Li2, Jiayan Lian3

  • 1Department of Radiation Oncology, The First Hospital of Lanzhou University, Lanzhou University, Lanzhou, Gansu 730000, PR China; The First School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu 730000, PR China.

Journal of Advanced Research
|September 21, 2023
PubMed
Abstract

Insights

This study reveals how CDK2 promotes triple-negative breast cancer radioresistance by phosphorylating TRIM32, leading to STAT3 activation. Targeting the CDK2/TRIM32/STAT3 pathway offers a promising strategy to overcome treatment resistance in TNBC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Radiotherapy is a key treatment for triple-negative breast cancer (TNBC), but radioresistance necessitates new therapeutic targets.
  • The precise mechanism of CDK2 in promoting TNBC radioresistance requires further elucidation.

Purpose of the Study:

  • To investigate the relationship between CDK2 and TRIM32 in TNBC.
  • To elucidate the regulatory mechanism of CDK2 and TRIM32 in TNBC radioresistance.

Main Methods:

  • Immunohistochemistry, Western blot, and PCR were used to analyze protein and mRNA levels.
  • CRISPR/Cas9 and shRNA were employed for gene knockout and knockdown.
  • GST pull-down, immunoprecipitation, and in vitro isomerization assays were performed.
  • Tumorigenesis studies validated findings in vitro.

Main Results:

  • TRIM32 was identified as a substrate of CDK2, with radiotherapy enhancing their binding and TRIM32 phosphorylation.
  • This process facilitates TRIM32 nuclear translocation, inhibiting dephosphorylated STAT3 and increasing STAT3 transcription.
  • Clinical data confirmed the correlation between CDK2/TRIM32/STAT3 pathway components and TNBC prognosis.

Conclusions:

  • The CDK2/TRIM32/STAT3 signaling pathway plays a critical role in TNBC radioresistance.
  • Targeting this pathway presents a potential therapeutic strategy to enhance radiotherapy efficacy in TNBC.
Keywords:
CDK2Nuclear translocationRadioresistanceTRIM32Triple-negative breast cancer

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