ArticleBiomolecules2026
Stroma-Dominant Colorectal Cancer Harbors CAF-Rich Spatial Architecture and EMT-Associated Cancer Cell Plasticity Detectable After Dissemination.
Article in Biomolecules, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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10 authors.
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Abstract
Colorectal cancers (CRCs) include stroma-dominant tumors with desmoplasia and differentiated, gland-forming tumors with little stroma. We asked whether this difference reflects stromal abundance alone or also involves a distinct cancer cell state. HEST-1K sections were classified as M-type (stroma-dominant; five patient/tissue units) or D-type (differentiated and cancer cell-dominant; seven units). Prespecified EMT/pEMT, ECM/integrin, YAP/TAZ-TEAD, and DTP/persister gene sets were examined across spatial, bulk, and single-cell datasets and patient-derived malignant ascites cultures. M-type tumors contained broader CAF-rich compartments and higher activity of all four programs in EPCAM/KRT-high regions, including epithelial-dense tumor cores. Activity was greatest near CAF-rich areas. In GSE39582, EMT/pEMT, ECM/integrin, DTP/persister, and invasive epithelial programs were independently associated with recurrence. Ascites-derived cultures from stroma-dominant tumors showed higher ECM/integrin and survival programs. Independent institutional analyses supported the public data findings: focused real-time PCR showed higher MAPK/TGF-beta-related gene expression in M-type-derived than in D-type-derived ascites cells, and IHC showed stronger epithelial CD44v6 expression in M-type primary tumors and metastatic lymph node lesions. CAF co-culture increased VIM-promoter activity. These findings characterize stroma-dominant CRC as a spatially organized ecosystem in which a CAF-rich compartment is associated with stress-adapted cancer cell programs. Its poor prognosis may therefore involve not only stromal abundance but also a morphology-associated cancer cell state detectable after dissemination.
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