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  • Title: Heparan Sulfate-Instructed Self-Assembly Selectively Inhibits Cancer Cell Migration.
    Author: Mang D, Roy SR, Zhang Q, Hu X, Zhang Y.
    Journal: ACS Appl Mater Interfaces; 2021 Apr 21; 13(15):17236-17242. PubMed ID: 33830729.
    Abstract:
    Heparan sulfate (HS) has important emerging roles in oncogenesis, which represents potential therapeutic strategies for human cancers. However, due to the complexity of the HS signaling network, HS-targeted synthetic cancer therapeutics has never been successfully devised. To conquer the challenge, we developed HS-instructed self-assembling peptides by decorating the "Cardin-Weintraub" sequence with aromatic amino acids. The HS-binding interactions induce localized accumulation of synthetic peptides triggering molecular self-assembly in the vicinity of highly expressed Heparan sulfate proteoglycans (HSPGs) on the cancer cell membrane. The nanostructures hinder the binding of HSPG with metastasis promoting protein-heparin-binding EGF-like growth factor (HBEGF) inhibiting the activation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK). Our study proved that HS-instructed self-assembly is a promising synthetic therapeutic strategy for targeted cancer migration inhibition.
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