TRIM29 facilitates the epithelial-to-mesenchymal transition and the progression of colorectal cancer via the activation of the Wnt/β-catenin signaling pathway

BackgroundTripartite Motif 29 (TRIM29) has been newly identified as being implicated in cancer progression. However, the biological role and molecular mechanism of TRIM29 in the invasion and metastasis of colorectal cancer (CRC) remain to be determined.MethodsThe expression levels of TRIM29 and -catenin in CRC patient specimens were detected by immunohistochemistry. Recombinant lentivirus vectors containing the TRIM29 gene and its small hairpin interfering RNAs were constructed and transduced into CRC cells. Wound-healing and Transwell assays were performed to evaluate the migration and invasion abilities of CRC cells in vitro. Hepatic metastasis models in nude mice were established to validate the function of TRIM29 in vivo. Moreover, the expressions of epithelial-to-mesenchymal transition (EMT)-associated proteins were detected by qRT-PCR and Western blotting in CRC cells. Finally, Western blotting, qRT-PCR, luciferase reporter assays, and immunofluorescence assays were used to explore the molecular mechanisms of TRIM29 in CRC progression.ResultsIncreased TRIM29 expression positively correlated with lymph node metastasis and -catenin expression in patient CRC tissues. Overexpression of TRIM29 promoted invasion and metastasis of CRC cells in vitro and in vivo by regulating EMT, whereas the knockdown of TRIM29 had the opposite effect. Further mechanistic studies suggest that TRIM29 can activate the Wnt/-catenin signaling pathway via up-regulating CD44 expression in colorectal cancer.ConclusionsTRIM29 induces EMT through activating the Wnt/-catenin signaling pathway via up-regulating CD44 expression, thus promoting invasion and metastasis of CRC.