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Integrin and Heparan Sulfate Dual-Targeting Peptide Assembly Suppresses Cancer Metastasis

Sona Rani Roy1, Guanying Li1, Xunwu Hu1

  • 1Bioinspired Soft Matter Unit, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Okinawa 904-0495, Japan.

ACS Applied Materials & Interfaces
|April 9, 2020
PubMed

Insights

Researchers developed a dual-targeting peptide assembly to inhibit cancer metastasis by targeting integrin β1 and heparan sulfate. This peptide assembly effectively reduces cancer cell migration and invasion, offering a promising nanomedicine strategy.

Area of Science:

  • Biochemistry
  • Nanomedicine
  • Cancer Biology

Background:

  • Metastasis remains a significant challenge in cancer therapy, with many treatments proving ineffective.
  • Upregulated expression of integrin β1 and heparan sulfate is observed in metastatic tumors.

Purpose of the Study:

  • To develop a novel peptide assembly targeting both integrin β1 and heparan sulfate (HS) to inhibit cancer metastasis.
  • To investigate the mechanism of action of the dual-targeting peptide on cancer cell migration and invasion.

Main Methods:

  • Development of a self-assembling peptide targeting integrin β1 and HS.
  • Investigation of peptide self-assembly into nanofibrous microdomains on cancer cell membranes.
  • Analysis of integrin clustering, actin cytoskeleton involvement, and yes-associated protein deactivation.

Main Results:

  • The dual-targeting peptide self-assembles into nanofibrous microdomains on cancer cell membranes.
  • This assembly triggers integrin clustering, leading to the deactivation of the oncogene yes-associated protein via the actin cytoskeleton.
  • Potent and dose-dependent inhibition of cancer cell migration and invasion was observed in multiple cancer cell lines, including pancreatic cancer.

Conclusions:

  • The developed integrin/HS dual-targeting peptide assembly effectively inhibits cancer metastasis.
  • This approach demonstrates a potential general design strategy for nanomedicine development based on nano-biointerface fabrication.
Keywords:
YAP inactivationcancer metastasisheparan sulfateintegrinpeptide assembly

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