PLK2 phosphorylates and inhibits enriched TAp73 in human osteosarcoma cells

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Zheng Bo Hu1, Xiao Hong Liao2, Zun Ying Xu1

  • 1Department of Orthopedics, Zhu Jiang Hospital of Southern Medical University, Guangzhou, Guangdong, 510280, China.

Cancer Medicine
|December 3, 2015
PubMed

Insights

Polo-like kinase 2 (PLK2) phosphorylates and inhibits the tumor suppressor TAp73 in osteosarcoma cells. Inhibiting PLK2 reactivates TAp73, suppressing tumor growth and promoting apoptosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • TAp73, a p53 family member, can compensate for p53 function in cancer cells.
  • TAp73's antitumor activity is regulated by its phosphorylation status.
  • Polo-like kinase 2 (PLK2) is implicated in bone development and potentially cancer.

Purpose of the Study:

  • To investigate the role of PLK2 in phosphorylating and regulating TAp73 function in osteosarcoma.
  • To determine if PLK2 inhibition can restore TAp73's antitumor activity.

Main Methods:

  • Bioinformatic analysis and phosphorylation prediction.
  • Co-immunoprecipitation to confirm physical binding of PLK2 and TAp73.
  • Site-directed mutagenesis to identify the phosphorylation site (Ser48).
  • Cell-based assays (mRNA expression, proliferation, apoptosis, cell cycle, invasion) in osteosarcoma cell lines (Saos2) with and without TAp73 knockdown.

Main Results:

  • PLK2 physically binds and phosphorylates TAp73 at Ser48, particularly when TAp73 is upregulated by cisplatin.
  • PLK2 inhibition, combined with cisplatin, significantly enhanced p21 and puma mRNA expression.
  • Inhibition of PLK2 in TAp73-enriched cells led to reduced proliferation, increased apoptosis, G1 arrest, and decreased invasion.
  • These effects were dependent on TAp73 presence, as TAp73 knockdown abolished the observed changes.

Conclusions:

  • PLK2 phosphorylates TAp73, inhibiting its tumor suppressor activity in osteosarcoma.
  • Targeting PLK2 represents a potential therapeutic strategy for osteosarcoma, especially in tumors overexpressing TAp73.
  • This study elucidates a novel mechanism regulating TAp73 function in cancer treatment.
Keywords:
AntitumorPLK2TAp73cisplatinphosphorylation

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