9NAB

Cryo-EM structure of the alpha5beta1 integrin headpiece with OS2966 Fab

Summary for 9NAB

• Entry DOI: 10.2210/pdb9nab/pdb
• EMDB information: 49184
• Descriptor: Integrin beta-1, Human Integrin alpha 5, IgG heavy chain, ... (4 entities in total)
• Functional Keywords: integrin antibody, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 178580.37

Authors

Wang, L.,Zhang, C. (deposition date: 2025-02-11, release date: 2025-07-23, Last modification date: 2026-02-18)

Primary citation

Song, N.,Chen, S.,Wang, L.,Dang, J.,Cao, X.,Singh, S.,Yang, L.,Wang, J.,Rosen, S.T.,Wang, Y.,Chen, C.D.,Zhang, C.,Feng, M.
ITGB1 Regulates Triple-Negative Breast Cancer Development by Modulating the Tumor Microenvironment.
Adv Sci, :e13672-e13672, 2026

PubMed Abstract: Tumorigenesis and metastasis are frequently attributed to the intricate interplay between cancer cells and the tumor microenvironment (TME). Comprehending the mechanisms and key regulators of cancer-immune crosstalk in the TME is imperative for developing efficacious immunotherapy. Through a series of in vivo CRISPR screens, we identified tumor-intrinsic ITGB1 as a critical regulator of triple-negative breast cancer (TNBC) development and deciphered its underlying mechanisms. Tumoral ITGB1 facilitated the establishment of pro-tumorigenic TME by orchestrating tumor-associated myeloid populations. Suppressing ITGB1 favored the enrichment of anti-tumorigenic myeloid cells and enhanced infiltration of CD4 and CD8 T cells, culminating in superior antitumor effects. CRISPR scanning pinpointed a previously unrecognized functional domain essential for ITGB1's pro-tumorigenic activity. This domain is distinct from all known ligand-binding sites in ITGB1. An antibody capable of sterically blocking this domain significantly impaired TNBC progression. These findings position tumoral ITGB1 as a promising therapeutic target for reprogramming the TME from a pro- to an anti-tumorigenic state, thereby effectively inhibiting TNBC development. Our study uncovers a novel mechanism of TNBC development and provides a unique therapeutic strategy for targeting ITGB1 in TNBC treatment.

PubMed: 41632816
DOI: 10.1002/advs.202513672

Experimental method

ELECTRON MICROSCOPY (2.54 Å)