FOSL1 promotes tumorigenesis in colorectal carcinoma by mediating the FBXL2/Wnt/β-catenin axis via Smurf1.

Colorectal carcinoma (CC), one of the most prevalent digestive cancers with high mortality and morbidity globally, still lacks powerful therapies to improve the prognosis. Here, we established that the expression of fos-like antigen-1 (Fosl1) was elevated in CC tissues versus adjacent tissues. Importantly, high Fosl1 expression was related to dismal prognosis among CC patients. Functional assays displayed that Fosl1 increased the viability, epithelial-to-mesenchymal transition (EMT), migration and invasion of CC cells. Additionally, a xenograft assay showed that silencing of Fosl1 in CC cells retarded lung, liver and kidney metastases in vivo. Further investigation demonstrated that Fosl1 was involved in malignant aggressiveness of CC cells by binding to smad ubiquitination regulatory factor 1 (Smurf1). Mechanistically, Smurf1-induced F-Box and leucine rich repeat protein 2 (FBXL2) ubiquitination resulted in its degradation, while FBXL2 disrupted the activation of the Wnt/β-catenin signaling. In summary, Fosl1 plays a pro-metastatic and carcinogenetic role in CC, and we provided forceful evidence that Fosl1 inhibition might act as a prognostic and therapeutic option in CC.