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PAQR4 has a tumorigenic effect in human breast cancers in association with reduced CDK4 degradation

Huanhuan Zhang1,2, Ruomei Han1,2, Zhi-Qiang Ling3

  • 1Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, China.

Carcinogenesis
|December 12, 2017
PubMed

Insights

Progestin and adipoQ receptor 4 (PAQR4) promotes breast cancer growth by increasing cell proliferation and tumor formation. It also affects cyclin-dependent kinases 4 (CDK4) protein levels, impacting patient survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Progestin and adipoQ receptor 4 (PAQR4) is part of a family involved in metabolism and cancer.
  • The role of PAQR4 in human cancers, particularly breast cancer, is not well understood.

Purpose of the Study:

  • To investigate the function of PAQR4 in human breast cancer development and progression.
  • To explore the molecular mechanisms underlying PAQR4's role in breast cancer.

Main Methods:

  • Analysis of PAQR4 expression in human breast cancer tissues using the ONCOMINE database and patient samples.
  • In vitro studies involving PAQR4 knockdown and overexpression in breast cancer cell lines (SUM159, MCF7) to assess proliferation and colony formation.
  • In vivo tumor xenograft models to evaluate the effect of PAQR4 on tumor growth.
  • Investigation of PAQR4's impact on cyclin-dependent kinases 4 (CDK4) protein levels, degradation, and polyubiquitination.

Main Results:

  • PAQR4 is significantly upregulated in human breast cancer tissues compared to normal tissues.
  • Higher PAQR4 mRNA levels correlate with poorer disease-free and overall survival in breast cancer patients.
  • PAQR4 overexpression enhances breast cancer cell proliferation, colony formation, and tumor growth in vivo.
  • PAQR4 knockdown suppresses these processes.
  • PAQR4 negatively regulates CDK4 protein levels by modulating its degradation and polyubiquitination.

Conclusions:

  • PAQR4 exhibits a tumorigenic effect in human breast cancer.
  • PAQR4's oncogenic role is linked to its modulation of CDK4 protein stability.
  • PAQR4 represents a potential therapeutic target for breast cancer treatment.

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