Cancer Cell International · Published 2026-06-12 · DOI 10.1186/s12935-026-04381-5
Viet Cuong Nguyen, Kuang-Chao Cheng, Thuy-Tien Thi Phan, Thi-Luu Ho, Yu-Hsin Lin, Li-Jen Kuo, Yao-An Shen, Chi-Long Chen
Abstract Background Multiple interacting factors within the tumor microenvironment, including mechanical pressure, extracellular matrix components, hypoxia, and vascular architecture, are known to promote cancer progression. Although fibronectin 1 functions as a critical extracellular matrix glycoprotein in colorectal cancer, its specific interaction with mechanical pressure is not well characterized. Methods This study utilized a meta-analysis (PROSPERO: CRD42024571414) alongside an in vitro weight-induced compression model to evaluate the prognostic role of fibronectin 1 and its interaction with mechanical pressure during colorectal cancer progression. Results The meta-analysis demonstrated significantly elevated fibronectin 1 expression in colorectal cancer patients compared to controls (SMD = 0.90, 95% CI: 0.56–1.25, P < 0.001) and a positive association with distant metastasis (OR = 3.63, 95% CI: 1.21–10.95, P = 0.0219). Analysis of colorectal cancer tissues versus adjacent normal tissues (n = 19) revealed markedly increased fibronectin 1 expression in both tumor cells and stromal components. Single-cell RNA sequencing analysis (GSE302903) identified FN1 expression in diverse cell populations, including cancer-associated fibroblasts, endothelial cells, macrophages, and tumor cells. Furthermore, high fibronectin 1 levels were established as a poor prognostic factor in colorectal cancer (HR = 2.47, 95% CI: 1.88–3.25, P < 0.001). In vitro experiments showed that pressure enhanced viability, proliferation, migration, and invasion of colorectal cancer cells and cancer stem cells through fibronectin 1. RNA sequencing indicated significant pressure-induced gene expression changes in colorectal cancer cells and identified the activation of multiple pathways. Specifically, the combined effect of pressure and fibronectin 1 upregulated of TGFBR1, SMAD2, SMAD4, and ROCK1 gene and p-SMAD2 expression. Conclusions The expression of fibronectin 1 predicts poor overall survival in colorectal cancer and, together with mechanical pressure, facilitates colorectal cancer progression.
Abstract from DOAJ. Public domain (CC0 1.0).
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Nguyen, V., Cheng, K., Phan, T., et al. (2026). Fibronectin 1 mediates pressure-induced aggressive phenotypes in colorectal cancer cells and cancer stem cells. Cancer Cell International. https://doi.org/10.1186/s12935-026-04381-5