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A peptide derived from adaptor protein STAP-2 inhibits tumor progression by downregulating epidermal growth factor

Taiga Maemoto1, Yuichi Kitai1, Runa Takahashi1

  • 1Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, Japan.

The Journal of Biological Chemistry
|November 21, 2022
PubMed

Insights

A novel peptide, 2D5, effectively blocks signal-transducing adaptor family member-2 (STAP-2) interactions with epidermal growth factor receptor (EGFR). This inhibition suppresses cancer cell proliferation and tumor growth in prostate and lung cancer models.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Biochemistry

Background:

  • Signal-transducing adaptor family member-2 (STAP-2) is an adaptor protein regulating intracellular signals.
  • STAP-2 binding to epidermal growth factor receptor (EGFR) enhances its stability and signaling, particularly in prostate cancer.
  • Targeting the STAP-2-EGFR interaction presents a potential therapeutic strategy for cancer treatment.

Purpose of the Study:

  • To investigate the potential of a STAP-2-derived peptide, 2D5, in inhibiting STAP-2-EGFR interactions.
  • To evaluate the efficacy of 2D5 peptide in suppressing cancer cell proliferation and tumor growth.
  • To elucidate the impact of 2D5 peptide on EGFR signaling pathways.

Main Methods:

  • Utilized a STAP-2-derived peptide (2D5) to block STAP-2-EGFR interactions.
  • Assessed the effect of 2D5 peptide on cancer cell proliferation in vitro.
  • Evaluated 2D5 peptide's impact on tumor growth using murine xenograft models of human prostate (DU145) and lung (A549) cancer.
  • Analyzed changes in EGFR signaling and stability upon 2D5 peptide treatment during EGF stimulation.

Main Results:

  • The 2D5 peptide successfully blocked STAP-2-EGFR interactions.
  • 2D5 peptide suppressed EGFR-mediated proliferation across multiple cancer cell lines.
  • In vivo studies demonstrated that 2D5 peptide inhibited tumor growth in both prostate and lung cancer xenograft models.
  • EGFR signaling and stability were significantly reduced by 2D5 peptide treatment.

Conclusions:

  • The 2D5 peptide is a promising novel anticancer agent.
  • 2D5 peptide effectively inhibits STAP-2-mediated activation of EGFR signaling.
  • This peptide demonstrates potential for suppressing prostate and lung cancer progression.
Keywords:
EGFRSTAT3adaptor proteinantitumor peptideprostate cancer

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