*Zoom*[PhD Thesis Presentation] - Ms. Sona Roy "Design Integrin-targeted Molecular Self-assembling Peptides for Cancer Migration Inhibition"

Presenter: Ms. Sona Roy

Supervisor: Professor Ye Zhang

Co-supervisor: Professor Mitsuhiro Yanagida

Audience: OIST researchers and students

Unit: Bioinspired Soft Matter Unit

Zoom Code: no more available

Title: Design Integrin-targeted Molecular Self-assembling Peptides for Cancer Migration Inhibition

Abstract:

The Yes-associated protein (YAP) is a major oncoprotein responsible for cancer metastasis. YAP’s oncogenic activity is regulated by both the Hippo kinase cascade and uniquely by a mechanical-force-induced actin remodeling process. Here, inspired by outside-in integrin activation via ligand-binding, we developed a molecular self-assembly (MSA) technology that selectively inhibit cancer cell migration by inactivating YAP through physical regulation mediated by actin cytoskeleton. Particularly, we designed a library of integrin-ligand-based peptides that upon binding with integrins, undergo self-assembly to form nanostructures specifically on plasma membrane of cancer cells. After characterizing the size and rigidity of the MSAs and confirming that their assembly does trigger formation of the integrin-talin-vinculin complexes that initiate actin cytoskeleton reorganization and inactivate YAP, we show in multiple cancer cell lines and in xenograft tumor models in mice that the MSAs exert potent, cancer-cell-specific, and dose-dependent anti-migration effects. Finally, we confirmed expected molecular consequences of the MSAs on YAP-related proteins like AMOT and on YAP target genes. Thus, our work illustrates how basic biochemical insights can be exploited as the basis for a nano-biointerface fabrication technology which links nanoscale protein activities at specific sub-cellular locations to both microscale and molecular biological activities to suppress cancer cell migration.