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PSMB5 plays a dual role in cancer development and immunosuppression

Chih-Yang Wang1,2, Chung-Yen Li1, Hui-Ping Hsu3

  • 1Department of Biochemistry and Molecular Biology, National Cheng Kung UniversityTainan, Taiwan, R.O.C.

American Journal of Cancer Research
|December 9, 2017
PubMed

Insights

High proteasome subunit β5 (PSMB5) expression fuels cancer growth and immune suppression. Silencing PSMB5 inhibits tumor progression and activates anti-cancer M1 macrophages, revealing PSMB5 as a promising therapeutic target for cancer immunotherapy.

Area of Science:

  • Oncology
  • Immunology
  • Bioinformatics

Background:

  • Tumor progression depends on cancer cell properties and the tumor microenvironment, including immune cells.
  • The proteasome subunit β5 (PSMB5) plays a role in both tumor cells and immune cells.
  • Targeting drugs that inhibit cancer cells and activate immune cells is crucial.

Purpose of the Study:

  • To investigate the role of the proteasome subunit β5 (PSMB5) in breast cancer.
  • To explore PSMB5 as a potential therapeutic target for cancer treatment and immunotherapy.

Main Methods:

  • Bioinformatic analysis of breast cancer databases (TCGA, METABRIC).
  • In vitro knockdown of PSMB5 in THP-1 monocytes and MDA-MB-231 cancer cells using shRNA.
  • In vivo studies using a subcutaneous mouse model with lentiviral delivery of PSMB5 shRNA.

Main Results:

  • High PSMB5 expression in breast cancer correlates with poor survival and M2 macrophage infiltration.
  • PSMB5 knockdown promoted M1 macrophage differentiation and inhibited cancer cell growth and migration.
  • PSMB5 shRNA delivery suppressed tumor growth in a mouse model.

Conclusions:

  • PSMB5 exhibits immunosuppressive and oncogenic characteristics, making it a viable cancer therapeutic target.
  • Targeting PSMB5 offers a novel strategy to enhance cancer immunotherapy by activating anti-tumor immunity.
Keywords:
Breast cancerPSMB5bioinformaticsmacrophageproteasome

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