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-Structure paper
| タイトル | ITGB1 Regulates Triple-Negative Breast Cancer Development by Modulating the Tumor Microenvironment. |
|---|---|
| ジャーナル・号・ページ | Adv Sci (Weinh), Vol. 13, Issue 20, Page e13672, Year 2026 |
| 掲載日 | 2026年2月3日 |
著者 | Nuozi Song / Siqi Chen / Lei Wang / Jessica Dang / Xu Cao / Stephanie Singh / Lu Yang / Jinhui Wang / Steven T Rosen / Yingyu Wang / Chun-Wei D Chen / Cheng Zhang / Mingye Feng / ![]() |
| PubMed 要旨 | 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- ...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. |
リンク | Adv Sci (Weinh) / PubMed:41632816 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.54 Å |
| 構造データ | EMDB-49184, PDB-9nab: |
| 由来 |
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キーワード | IMMUNE SYSTEM / Integrin antibody |
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