ArticleNature structural & molecular biology2024
A novel class of inhibitors that disrupts the stability of integrin heterodimers identified by CRISPR-tiling-instructed genetic screens.
Article in Nature structural & molecular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 18 citations in OpenAlex.
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- PARP1-mediated 5' flap dynamics facilitate Okazaki fragment maturation.bioRxiv : the preprint server for biology · 2026Article
- ITGB1 Regulates Triple-Negative Breast Cancer Development by Modulating the Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Unraveling the αVβ5-GLUT5 axis in breast cancer: linking extracellular matrix signaling to fructose metabolism: a scoping review.Molecular biology reports · 2026Article
- FCHo2, not talin, enables inside-out activation of integrin ɑvβ5 in curved adhesions.Nature communications · 2026Article
- Integrin inhibition facilitates fibrocartilaginous transformation in connective tissue in osteoarthritis.Science advances · 2026Article
- Genetically prioritized plasma proteins in intracerebral hemorrhage identified by Mendelian randomization with functional evidence of neuronal vulnerability.American journal of translational research · 2026Article
- FCHo2, instead of talin, enables inside-out activation of integrin ɑvβ5 in curved adhesions.bioRxiv : the preprint server for biology · 2025Article
- Article
- Nuclear Control of Mitochondrial Homeostasis and Venetoclax Efficacy in AML via COX4I1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- CRISPR screening reveals ZNF217 as a vulnerability in high-risk B-cell acute lymphoblastic leukemia.Theranostics · 2025Article
- Collagen I Increases Palmitate-Induced Lipotoxicity in HepG2 Cells via Integrin-Mediated Death.Biomolecules · 2024Article
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- Dual inhibitory potential of ganoderic acid A on GLUT1/3: computational andRSC advances · 2024Article
- Regulation of the Degradation Properties of Tyrosinase-Catalyzed Crosslinking Silk Membranes for Superficial Wound Repair.Materials (Basel, Switzerland) · 2024Article
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Authors and funding
27 authors at 3 institutions in 2 countries.
Funding
Abstract
The plasma membrane is enriched for receptors and signaling proteins that are accessible from the extracellular space for pharmacological intervention. Here we conducted a series of CRISPR screens using human cell surface proteome and integrin family libraries in multiple cancer models. Our results identified ITGAV (integrin αV) and its heterodimer partner ITGB5 (integrin β5) as the essential integrin α/β pair for cancer cell expansion. High-density CRISPR gene tiling further pinpointed the integral pocket within the β-propeller domain of ITGAV for integrin αVβ5 dimerization. Combined with in silico compound docking, we developed a CRISPR-Tiling-Instructed Computer-Aided (CRISPR-TICA) pipeline for drug discovery and identified Cpd_AV2 as a lead inhibitor targeting the β-propeller central pocket of ITGAV. Cpd_AV2 treatment led to rapid uncoupling of integrin αVβ5 and cellular apoptosis, providing a unique class of therapeutic action that eliminates the integrin signaling via heterodimer dissociation. We also foresee the CRISPR-TICA approach to be an accessible method for future drug discovery studies.
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