TRIM14 promotes colorectal cancer cell migration and invasion through the SPHK1/STAT3 pathway.

Background: Colorectal cancer (CRC) is one of the most lethal malignancies. Tripartite Motif Containing 14 (TRIM14) is a member of TRIM family proteins, which are involved in the pathogenesis of various cancers. This study aimed to investigate TRIM14 expression in CRC tissues, and its effects on the migration and invasion of CRC cell lines.

Methods: TRIM14 mRNA expression was detected by real-time PCR analysis. Cell migration and invasion were measured by Transwell assays. Protein expression was assessed by western blot analysis.

Results: The expression of TRIM14 was significantly higher in CRC tissues than in matched non-cancerous tissues. TRIM14 knockdown by specific short hairpin RNA (shRNA) attenuated CRC cell migration and invasion, whereas TRIM14 overexpression caused reverse effect. Moreover, TRIM14 positively regulated the protein levels of sphingosine kinase 1 (SPHK1) and phosphorylated STAT3 (p-STAT3), as well as the mRNA and protein expression of matrix metalloproteinase 2, MMP9 and vascular endothelial growth factor, which are transcriptional targets of the STAT3 signaling pathway. Importantly, the blockage of the SPHK1/STAT3 signaling pathway by SKI-II or AG490 could reverse the TRIM14-promoted CRC cell migration and invasion.

Conclusions: Our results reveal a critical role for TRIM14 in promoting migration and invasion of CRC cells, and suggest TRIM14 may serve as a potential molecular target to prevent CRC metastasis.