Identification of asporin as a HER3 ligand exposes a therapeutic vulnerability in prostate cancer.
1/5 보강
Cancer-associated fibroblasts (CAFs) are part of the tumor microenvironment (TME) that enable cancer cells to establish metastases, but the mechanisms of these interactions are not fully known.
APA
Hesterberg AB, Wong HY, et al. (2025). Identification of asporin as a HER3 ligand exposes a therapeutic vulnerability in prostate cancer.. JCI insight, 10(16). https://doi.org/10.1172/jci.insight.187151
MLA
Hesterberg AB, et al.. "Identification of asporin as a HER3 ligand exposes a therapeutic vulnerability in prostate cancer.." JCI insight, vol. 10, no. 16, 2025.
PMID
40857406 ↗
Abstract 한글 요약
Cancer-associated fibroblasts (CAFs) are part of the tumor microenvironment (TME) that enable cancer cells to establish metastases, but the mechanisms of these interactions are not fully known. Herein, we identified a paracrine mechanism in which CAF-secreted asporin (ASPN) activated ErbB signaling and subsequent migration of adjacent prostate cancer cells. Our data support that ASPN bound directly to the ligand binding domain of human epidermal growth factor 3 (HER3) and induced HER2/HER3 heterodimerization and activation of the PI3K, MAPK, and calcium pathways. Genetic and therapeutic inhibition of HER2/HER3 ablated ASPN-induced signaling and migration. Clinically, ASPN was detected in the stroma of HER2/HER3-expressing human metastatic prostate cancer, supporting the clinical relevance of these findings and highlighting a potential therapeutic vulnerability. Antibody-drug conjugate (ADC) therapies designed to target HER2 (trastuzumab-deruxtecan) or HER3 (patritumab-deruxtecan) significantly diminished prostate cancer cell growth in vitro and tumor size in vivo, despite Aspn in the TME. Collectively, these findings indicate ASPN functions as a HER3 ligand to induce cellular migration, and inhibition with anti-HER2 or anti-HER3 ADC therapies highlights potential clinical utility for patients with metastatic castration-resistant prostate cancer that expresses HER2 or HER3.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
- Male
- Humans
- Receptor
- ErbB-3
- Prostatic Neoplasms
- Tumor Microenvironment
- Cell Line
- Tumor
- Ligands
- Erb-b2 Receptor Tyrosine Kinases
- Animals
- Mice
- Cell Movement
- Cancer-Associated Fibroblasts
- Saporins
- Signal Transduction
- Xenograft Model Antitumor Assays
- Trastuzumab
- Extracellular Matrix Proteins
- Cell biology
- Oncogenes
- Oncology
- Prostate cancer
- Signal transduction
🏷️ 같은 키워드 · 무료전문 — 이 논문 MeSH/keyword 기반
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