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The deubiquitinating enzyme USP11 regulates breast cancer progression by stabilizing PGAM5

Nannan Zhang1, Quhui Wang1, Yunpeng Lu1

  • 1Department of General Surgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226000, China.

Breast Cancer Research : BCR
|September 19, 2024
PubMed

Insights

This study reveals that Phosphoglycerate mutase 5 (PGAM5) is significantly expressed in breast cancer, driving proliferation and metastasis. The ubiquitin-specific protease 11 (USP11) protein stabilizes PGAM5, impacting cancer progression and offering potential new therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Breast cancer is a prevalent global malignancy.
  • The role of Phosphoglycerate mutase 5 (PGAM5) in breast cancer is not well-defined.
  • Ubiquitin-specific protease 11 (USP11) influences breast cancer cell growth and metastasis.

Purpose of the Study:

  • To investigate the expression and function of PGAM5 in breast cancer.
  • To elucidate the regulatory mechanism of PGAM5 by USP11.
  • To explore the potential of the USP11/PGAM5 axis as a therapeutic target.

Main Methods:

  • Analysis of PGAM5 expression in breast cancer tissues.
  • In vitro and in vivo studies involving overexpression and knockdown of USP11 and PGAM5.
  • Investigation of protein stabilization mechanisms (de-ubiquitination and proteasomal degradation).
  • Assessment of ferroptosis-related protein activation.

Main Results:

  • PGAM5 is significantly expressed in breast cancer and promotes cell proliferation, invasion, and regulates ferroptosis.
  • USP11 stabilizes PGAM5 through de-ubiquitination, preventing its degradation.
  • The USP11/PGAM5 complex enhances breast cancer progression by activating iron death-related proteins.
  • USP11 and PGAM5 expression levels correlate with disease outcomes.

Conclusions:

  • PGAM5 plays a critical role in breast cancer progression.
  • USP11 stabilizes PGAM5, contributing to tumor growth and metastasis.
  • The USP11/PGAM5 interaction represents a potential biomarker and therapeutic strategy for breast cancer.
Keywords:
Breast cancerFerroptosisPGAM5USP11

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