Products Cited in Publications Worldwide FOXC1 promotes EMT and colorectal cancer progression by attracting M2 macrophages via the TGF-β/Smad2/3/snail pathway

FOXC1 promotes EMT and colorectal cancer progression by attracting M2 macrophages via the TGF-β/Smad2/3/snail pathway

Zhang, Haoran; Nie, Jinlin; Bao, Zhen; Shi, Yangdong; Gong, Jin; Li, Hailiang

DOI: PMID:

Abstract

Colorectal cancer is a highly prevalent and deadly malignancy worldwide. Current treatment strategies, including surgery, chemotherapy, and targeted therapy, still face limitations due to recurrence and metastasis. By conducting a weighted gene coexpression network analysis on gene expression data from The Cancer Genome Atlas, we pinpointed critical genes linked to M2 macrophages and tumor metastasis. Among these, FOXC1 emerged as a significant prognostic indicator within our predictive model. Clinical sample analysis further confirmed that FOXC1 is upregulated in colorectal cancer tissues and associated with an unfavorable patient outcome. Both in vivo and in vitro experimental results revealed that FOXC1 promotes CRC cell migration, invasion and proliferation by regulating the expression of Snail and TGF-β/Smad2/3 pathways, thereby facilitating the epithelial–mesenchymal transition process. Additionally, FOXC1 recruits M2 macrophages to the tumor microenvironment by regulating CXCL2 expression through Snail. The TGF-β factor secreted by M2 macrophages further activates the TGF-β/Smad2/3 pathway, forming a positive feedback loop. In these processes, FOXC1 plays a critical regulatory role. In summary, this study highlights the critical significance of FOXC1 in CRC progression and indicates its viability as a therapeutic target, offering a novel theoretical foundation for the development of future CRC treatment strategies.

Keywords

Colorectal cancer ; WGCNA ; FOXC1 ; Epithelial–mesenchymal transition ; TGF-β/Smad2/3 signalling pathway ; Macrophages

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