A cell-state axis underlying colonization in carcinomas with implications for metastasis risk prediction and interception.
1/5 보강
Metastasis to the liver drives mortality in pancreatic ductal adenocarcinoma (PDAC), yet mechanisms of colonization remain unclear.
APA
Handler JS, Li Z, et al. (2025). A cell-state axis underlying colonization in carcinomas with implications for metastasis risk prediction and interception.. Cell reports, 44(12), 116701. https://doi.org/10.1016/j.celrep.2025.116701
MLA
Handler JS, et al.. "A cell-state axis underlying colonization in carcinomas with implications for metastasis risk prediction and interception.." Cell reports, vol. 44, no. 12, 2025, pp. 116701.
PMID
41401069 ↗
Abstract 한글 요약
Metastasis to the liver drives mortality in pancreatic ductal adenocarcinoma (PDAC), yet mechanisms of colonization remain unclear. Using genomic barcoding, we developed a clonal competition model under immune surveillance, isolating murine PDAC subclones with high or low liver-colonization potential. Combined transcriptome and chromatin-accessibility analyses revealed a distinct "metastatic-potential axis," separate from the normal-to-PDAC and classical-basal axes. We established "MetScore" as a biomarker of this axis. MetScore distinguishes metastases from primary PDAC tumors in patients, predicts outcomes beyond classical-basal classifications, and generalizes across carcinoma subtypes, suggesting conserved colonization mechanisms. High-MetScore PDAC cells preferentially occupy immune cell-enriched niches, suggesting they remodel the metastatic microenvironment. Functional screening identified c-Fos as a positive mediator of colonization and a candidate anti-metastatic target. Collectively, we identify a cell-state axis underpinning PDAC liver colonization, introduce MetScore as a broadly applicable biomarker, and nominate actionable targets for peri-operative therapeutic intervention.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
- Animals
- Humans
- Mice
- Carcinoma
- Pancreatic Ductal
- Pancreatic Neoplasms
- Liver Neoplasms
- Neoplasm Metastasis
- Tumor Microenvironment
- Cell Line
- Tumor
- Proto-Oncogene Proteins c-fos
- Gene Expression Regulation
- Neoplastic
- Biomarkers
- CP: Cancer
- PDAC metastasis
- c-Fos
- carcinoma metastasis pathways
- intratumoral heterogeneity
- lineage barcoding
- metastasis biomarker
- metastatic potential
- pancreatic cancer
… 외 2개
🏷️ 같은 키워드 · 무료전문 — 이 논문 MeSH/keyword 기반
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