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Targeting the USP7-CDK1 axis suppresses estrogen receptor-positive breast cancer progression

Joseph Lin1,2, Yueh-Te Lin3, Kai-Wen Hsu4,5,6

  • 1Cancer Research Center, Changhua Christian Hospital, Changhua, 500, Taiwan, R.O.C.

Cancer Cell International
|February 21, 2025
PubMed

Insights

Targeting USP7 and CDK1 shows promise for treating advanced estrogen receptor-positive breast cancer (ERPBC). Inhibiting these targets can reduce tumor progression, metastasis, and overcome endocrine resistance in ERPBC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Estrogen receptor-positive breast cancer (ERPBC) is the most common type globally.
  • While treatments exist, new targets are crucial for metastatic or endocrine-resistant ERPBC.
  • USP7 is implicated in promoting ERPBC progression and metastasis.

Purpose of the Study:

  • To investigate the role of USP7 in ERPBC.
  • To explore USP7 as a therapeutic target for advanced ERPBC.
  • To evaluate the combined inhibition of USP7 and CDK1.

Main Methods:

  • Assessing USP7 expression in ERPBC.
  • Inhibiting USP7 activity and observing effects on proliferation, apoptosis, migration, and epithelial-mesenchymal transition.
  • Mass spectrometry to identify USP7 targets.
  • Investigating USP7-CDK1 interaction.
  • Evaluating combined USP7 and CDK1 inhibition using specific drugs.

Main Results:

  • USP7 is highly expressed in ERPBC and drives tumor progression and metastasis.
  • USP7 inhibition suppressed proliferation, induced apoptosis, and reversed epithelial-mesenchymal transition.
  • USP7 regulates CDK1 expression and stability; both are linked to poor survival in ERPBC.
  • Combined USP7 and CDK1 inhibition synergistically reduced malignant processes and metastasis.

Conclusions:

  • USP7 is a key driver of ERPBC progression and metastasis.
  • Targeting USP7, particularly in combination with CDK1, offers a potential strategy for overcoming endocrine resistance in advanced ERPBC.
Keywords:
CDK1DeubiquitinationEstrogen receptor-positive breast cancerTumor progressionUSP7

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