ARL4C is associated with epithelial-to-mesenchymal transition in colorectal cancer

Background: ADP-ribosylation factor-like protein 4C (ARL4C) is a member of the ARF small GTP-binding protein subfamily. The ARL4C gene is highly expressed in colorectal cancer (CRC). ARL4Cprotein promotes cell motility, invasion, and proliferation. Methods: : We investigated the characteristics of ARL4C by comparing its expression at the invasion front and relationshipswith clinicopathological data using RNAscope, a highly sensitive RNA in situ method. Results: : In all cases, ARL4C expression was observed in both cancer stromal cells and cancer cells. ARL4C expression in cancer cells was localized at the invasion front. In cancer stromal cells, ARL4C expression was significantly stronger in cases with high-grade tumor budding than in cases with low-grade tumor budding (P=0.0002). Additionally, ARL4C expression was significantly increased in patients with highhistological grade compared with those with lowhistological grade (P=0.0227). Furthermore, ARL4C expression was significantly stronger in lesions with the epithelial-to-mesenchymal transition (EMT) phenotype compared with the non-EMT phenotype (P=0.0289). In CRC cells, ARL4C expression was significantly stronger in cells that had the EMT phenotype compared with those with a non-EMT phenotype (P=0.0366). ARL4C expression was significantly higher in cancer stromal cells than in CRC cells (P<0.0001). Conclusion: Our analysis reinforces the possibility that ARL4C expression worsens prognosis. Further elucidation of the function of ARL4C is desired.