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00085472can124718-sup-figure_1.pdf (1.48 MB)

Supplementary Figure 1 from FGFR4 Promotes Stroma-Induced Epithelial-to-Mesenchymal Transition in Colorectal Cancer

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posted on 2023-03-30, 21:55 authored by Rui Liu, Jingyi Li, Ke Xie, Tao Zhang, Yunlong Lei, Yi Chen, Lu Zhang, Kai Huang, Kui Wang, Hong Wu, Min Wu, Edouard C. Nice, Canhua Huang, Yuquan Wei

PDF file, 1512K, Co-culture with TAFs induces a stem cell-like phenotype of colorectal cancer cells.

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ARTICLE ABSTRACT

Tumor cells evolve by interacting with the local microenvironment; however, the tumor–stroma interactions that govern tumor metastasis are poorly understood. In this study, proteomic analyses reveal that coculture with tumor-associated fibroblasts (TAF) induces significant overexpression of FGFR4, but not other FGFRs, in colorectal cancer cell lines. Mechanistic study shows that FGFR4 plays crucial roles in TAF-induced epithelial-to-mesenchymal transition (EMT) in colorectal cancer cell lines. Accumulated FGFR4 in cell membrane phosphorylates β-catenin, leading to translocation of β-catenin into the nucleus. Further, TAF-derived CCL2 and its downstream transcription factor, Ets-1, are prerequisites for TAF-induced FGFR4 upregulation. Furthermore, FGFR4-associated pathways are shown to be preferentially activated in colorectal tumor samples, and direct tumor metastasis in a mouse metastasis model. Our study shows a pivotal role of FGFR4 in tumor–stroma interactions during colorectal cancer metastasis, and suggests novel therapeutic opportunities for the treatment of colorectal cancer. Cancer Res; 73(19); 5926–35. ©2013 AACR.

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