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p53 suppression is essential for oncogenic SPAG5 upregulation in lung adenocarcinoma

Tong Wang1, Kaimi Li1, Hongyong Song1

  • 1Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Biochemical and Biophysical Research Communications
|April 9, 2019
PubMed

Insights

Sperm-associated antigen 5 (SPAG5) is upregulated in lung adenocarcinoma, promoting tumor growth. Targeting the p53-p21-SPAG5 pathway with MDM2 inhibitors offers a potential therapeutic strategy for lung cancer.

Area of Science:

  • Oncology
  • Molecular Biology

Background:

  • Aberrant sperm-associated antigen 5 (SPAG5) expression is linked to oncogenesis.
  • The specific role of SPAG5 in lung adenocarcinoma pathogenesis is not well understood.

Purpose of the Study:

  • To investigate the function of SPAG5 in lung adenocarcinoma.
  • To explore the regulatory mechanism of SPAG5 expression by the p53 pathway.

Main Methods:

  • Analysis of SPAG5 expression in lung adenocarcinoma cell lines.
  • In vitro and in vivo experiments involving SPAG5 knockdown.
  • Treatment with MDM2 inhibitor Nutlin-3a in wild-type p53 and p53-null lung cancer cells.
  • Assessment of p53 and p21 expression and their role in SPAG5 regulation.

Main Results:

  • SPAG5 is upregulated in lung adenocarcinoma cells compared to normal cells.
  • SPAG5 knockdown inhibits lung adenocarcinoma cell proliferation, colony formation, migration, and tumor growth.
  • Nutlin-3a treatment suppresses SPAG5 expression in p53 wild-type cells, dependent on the p53-p21 axis.
  • SPAG5 expression is regulated by the p53-p21 signaling pathway.

Conclusions:

  • Upregulated SPAG5 drives lung tumor progression.
  • SPAG5 is a potential prognostic marker for lung adenocarcinoma.
  • Targeting the p53-p21-SPAG5 axis presents a promising therapeutic avenue for lung cancer treatment.
Keywords:
Lung adenocarcinomaNutlin-3aSPAG5p53 pathway

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