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USP17 Suppresses Tumorigenesis and Tumor Growth through Deubiquitinating AEP

Xi Chen1, Chen Wang2, Keman Liao3

  • 1CAS key laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200025, China.

International Journal of Biological Sciences
|March 26, 2019
PubMed

Insights

Ubiquitin-specific protease 17 (USP17) acts as a tumor suppressor in breast cancer by deubiquitinating Asparaginyl endopeptidase (AEP), reducing its levels and inhibiting tumor growth via ERK signaling. This suggests USP17 as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Ubiquitin-specific protease 17 (USP17) is a deubiquitinase implicated in various solid tumors.
  • The precise role of USP17 in breast cancer development remains unclear.

Purpose of the Study:

  • To investigate the expression and function of USP17 in breast cancer.
  • To elucidate the molecular mechanism by which USP17 influences breast cancer tumorigenesis.

Main Methods:

  • Quantitative analysis of USP17 mRNA levels in breast cancer tissues and cell lines.
  • In vitro and in vivo experiments involving USP17 inhibition and overexpression.
  • Co-immunoprecipitation assays to identify USP17 interacting proteins.
  • Western blotting to assess protein levels and signaling pathways (ERK).

Main Results:

  • USP17 mRNA levels were lower in breast cancer tissues compared to normal tissues.
  • USP17 expression inversely correlated with malignancy in breast cancer cell lines.
  • USP17 inhibition promoted, while USP17 overexpression suppressed, breast cancer cell growth in vitro and in vivo.
  • USP17 directly interacted with and deubiquitinated Asparaginyl endopeptidase (AEP), leading to reduced AEP protein levels.
  • AEP knockdown inhibited breast cancer growth by inactivating ERK signaling.

Conclusions:

  • USP17 functions as a tumor suppressor in breast cancer.
  • USP17 inhibits breast cancer progression by deubiquitinating AEP, reducing its levels, and subsequently impacting ERK signaling.
  • USP17 represents a potential therapeutic target, and AEP a promising therapeutic target in breast cancer treatment.
Keywords:
AEPBreast cancerDeubiquitinationERKUSP17

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