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Inhibition of pressure-activated cancer cell adhesion by FAK-derived peptides

Bixi Zeng1,2,3, Dinesh Devadoss1,2, Shouye Wang1

  • 1Department of Surgery, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota, United States.

Oncotarget
|December 13, 2017
PubMed

Insights

Blocking FAK-Akt1 interaction with a novel peptide may prevent cancer metastasis during surgery. This targeted approach inhibits tumor cell adhesion and dissemination, offering a safer alternative to broad FAK or AKT inhibitors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Surgical Innovation

Background:

  • Cancer metastasis is often potentiated by surgical stress, involving FAK-Akt1 signaling and tumor cell adhesion.
  • Current treatments targeting FAK or AKT can cause systemic toxicity, necessitating more specific interventions.

Purpose of the Study:

  • To investigate if inhibiting FAK-Akt1 interaction can prevent perioperative tumor dissemination.
  • To identify and utilize a specific peptide sequence that disrupts FAK-Akt1 binding.

Main Methods:

  • Serial truncation and mutagenesis of FAK to identify a peptide that competes with Akt1.
  • Adenoviral delivery of the FAK-derived peptide in SW620 colon cancer cells under increased pressure.
  • Assessing cancer cell adhesion to collagen-I and murine surgical wounds.
  • Evaluating tumor-free survival in mice after tumor cell exposure during simulated surgical conditions.

Main Results:

  • The FAK-derived peptide successfully inhibited pressure-induced FAK phosphorylation and FAK-Akt1 co-immunoprecipitation.
  • Adenoviral FAK-derived peptide expression prevented pressure-induced adhesion of SW620 cells to surfaces and surgical wounds.
  • In vivo, the FAK-derived peptide significantly improved tumor-free survival in mice exposed to pressure-treated cancer cells.

Conclusions:

  • Targeting the FAK-Akt1 interaction with a specific peptide can effectively inhibit perioperative tumor cell adhesion and metastasis.
  • This peptide-based strategy offers a promising, targeted approach to reduce cancer spread during surgery without systemic toxicity.
  • Analogs of this 7-amino acid FAK-derived peptide could be developed as novel anti-metastatic therapeutics.
Keywords:
Akt1FAKmechanotransductionmetastasiswound recurrence

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