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TRIM21 is a novel regulator of Par-4 in colon and pancreatic cancer cells

Jeffrey Q Nguyen1, Rosalyn B Irby1

  • 1a Department of Medicine and Penn State Hershey Cancer Institute , Penn State College of Medicine , Hershey , PA , USA.

Cancer Biology & Therapy
|November 11, 2016
PubMed

Insights

Researchers discovered TRIM21 regulates prostate apoptosis response protein 4 (Par-4) levels, impacting cancer cell resistance to cisplatin. This finding identifies TRIM21 as a potential therapeutic target and prognostic marker for pancreatic cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Prostate apoptosis response protein 4 (Par-4) is a known tumor suppressor inducing cancer-cell selective apoptosis.
  • Understanding Par-4 regulation is crucial for identifying novel therapeutic targets in cancer treatment.
  • Novel regulators of Par-4 are underexplored, presenting an opportunity for therapeutic development.

Purpose of the Study:

  • To identify novel regulators of Par-4.
  • To investigate the interaction between TRIM21 and Par-4.
  • To determine the role of TRIM21-Par-4 interaction in cancer cell response to cisplatin and patient survival.

Main Methods:

  • Co-immunoprecipitation in colon cancer cells followed by mass spectrometry.
  • Endogenous interaction studies and domain analysis (PRY-SPRY).
  • Assessment of TRIM21's effect on Par-4 levels and cisplatin resistance; analysis of TRIM21 expression in pancreatic cancer patient survival data.

Main Results:

  • TRIM21 was identified as a novel interacting partner of Par-4.
  • TRIM21 downregulates Par-4 levels in response to cisplatin, increasing colon cancer cell resistance.
  • Forced Par-4 expression sensitizes pancreatic cancer cells to cisplatin, and TRIM21 expression predicts patient survival.

Conclusions:

  • TRIM21 negatively regulates Par-4, influencing cancer cell response to chemotherapy.
  • TRIM21 represents a novel prognostic marker for pancreatic cancer.
  • Targeting the TRIM21-Par-4 interaction could be a potential therapeutic strategy for pancreatic cancer.
Keywords:
CisplatinPar-4TRIM21colon cancerpancreatic cancerprognosisproteasome

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