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HspBP1 is a dual function regulatory protein that controls both DNA repair and apoptosis in breast cancer cells

Cha Kyung Youn1,2, Jung-Hee Lee1,3, Gurusamy Hariharasudhan1

  • 1DNA Damage Response Network Center, Chosun University School of Medicine, 375 Seosuk-dong, Gwangju, Republic of Korea.

Cell Death & Disease
|April 7, 2022
PubMed

Insights

Hsp70-binding protein 1 (HspBP1) suppresses breast cancer by regulating BRCA1 and DNA repair. Decreased HspBP1 in advanced cancers promotes genomic instability and radiation resistance.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Hsp70-binding protein 1 (HspBP1) is a co-chaperone regulating Hsp70, with poorly understood biological roles.
  • Breast cancer progression and treatment resistance are complex processes involving genetic instability and DNA repair mechanisms.

Purpose of the Study:

  • To investigate the role of HspBP1 in breast cancer tumorigenesis and its relationship with BRCA1.
  • To elucidate the mechanisms by which HspBP1 influences tumor suppression and response to ionizing radiation.

Main Methods:

  • Gene knockdown and overexpression in BRCA1-proficient and deficient breast cancer cell lines.
  • In vitro assays for anchorage-independent cell growth.
  • Xenograft models for in vivo tumor formation assessment.
  • Analysis of HspBP1 interactions with BRCA1 and DNA repair pathways.
  • Investigation of HspBP1's effect on Hsp70 and apoptosis-related proteins.

Main Results:

  • HspBP1 modulation significantly altered tumorigenesis in BRCA1-proficient cells but not in BRCA1-deficient cells.
  • HspBP1 interacts with BRCA1, promoting homologous recombination DNA repair and maintaining genomic stability.
  • HspBP1 enhances cell survival following ionizing radiation by interfering with Hsp70-apoptotic protease-activating factor-1 complex formation, independent of BRCA1 status.

Conclusions:

  • HspBP1 acts as a tumor suppressor in breast cancer, particularly in BRCA1-proficient contexts, by enhancing DNA repair and genomic stability.
  • Reduced HspBP1 expression, observed in high-grade and metastatic breast cancers, contributes to genomic instability and resistance to ionizing radiation therapy.
  • HspBP1 represents a potential therapeutic target for improving breast cancer treatment outcomes.

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