Peptide PDHPS1 Inhibits Ovarian Cancer Growth through Disrupting YAP Signaling

Xinxing Pan1, Zhe Geng1, Jingyun Li2

  • 1Department of Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, China.

Insights

The endogenous peptide PDHPS1 inhibits ovarian cancer growth by targeting the YAP signaling pathway. This novel antitumor peptide shows no observable side effects on normal tissues.

Area of Science:

  • Oncology
  • Molecular Biology
  • Peptide Therapeutics

Background:

  • Ovarian cancer metastasis and drug resistance pose significant threats to patients.
  • Endogenous peptides are emerging as promising therapeutic agents in oncology.
  • Few anti-ovarian cancer peptides have been identified, highlighting a need for new therapeutic strategies.

Purpose of the Study:

  • To investigate the biological roles and mechanism of the endogenous peptide PDHPS1 in ovarian cancer development.
  • To evaluate the therapeutic potential of PDHPS1 against ovarian cancer.

Main Methods:

  • In vitro and in vivo studies to assess PDHPS1's effect on ovarian cancer cell proliferation and tumor growth.
  • Peptide pull-down assays, mass spectrometry, Western blot, and qRT-PCR to identify PDHPS1's molecular targets.
  • Flow cytometry, cell membrane permeability tests, and IHC staining to evaluate PDHPS1's safety profile.

Main Results:

  • PDHPS1 significantly reduced ovarian cancer cell proliferation in vitro and inhibited tumor growth in vivo.
  • PDHPS1 binds to protein phosphatase 2 phosphatase activator (PTPA), increasing phosphorylated YAP and suppressing its downstream target genes.
  • PDHPS1 demonstrated no observable side effects on normal ovarian epithelium and hepatorenal function.

Conclusions:

  • The endogenous peptide PDHPS1 acts as an antitumor agent by inhibiting the YAP signaling pathway through interaction with PTPA in ovarian cancer.
  • PDHPS1 represents a potential therapeutic candidate for ovarian cancer treatment.
  • Modifications to enhance membrane penetration could further improve PDHPS1's therapeutic efficacy.

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