Original ArticleRufy3 promotes metastasis through epithelial-mesenchymal transition in colorectal cancer

- CRC tissues express higher levels of Rufy3 protein than normal tissues.
- Increased Rufy3 expression correlated with tumour progression and poor prognosis of CRC patients.
- High expression of Rufy3 promotes invasion and metastasis via EMT of CRC cell.
- Silencing of Rufy3 reverses EMT and diminishes the invasion of 5-FU-treated cells.
- Rufy3 is required for TGF-β1-induced EMT and cell migration in CRC.

Rufy3 is a RUN domain-containing protein that has been associated with gastric cancers; however, the role of Rufy3 in the progression of colorectal cancer (CRC) remains unknown. We demonstrated that Rufy3 expression was higher in 11/12 fresh CRC tissues than in adjacent normal tissues. Rufy3 induced elevated expression and transactivity of four major oncogenes in CRC. Moreover, siRNA-mediated repression of Rufy3 induced G0/G1 cell cycle arrest, and Rufy3 overexpression enhanced CRC cell proliferation in vitro and in vivo. Furthermore, Rufy3 up-regulation promoted epithelial-mesenchymal transition (EMT) and metastatic phenotypes. Using an established in vitro cell model of 5-fluorouracil-resistant (5-FU) CRC cells, we assessed cellular morphology, molecular changes, and invasion and found that these characteristics were consistent with EMT. Silencing of Rufy3 by siRNA reversed EMT and greatly diminished the invasion of 5-FU-treated cells. In addition, TGF-β1 induced Rufy3 expression in a dose-dependent manner, and Rufy3 knockdown inhibited TGF-β1-induced EMT. In vivo, higher expression of Rufy3 promoted CRC cell invasion and metastasis and induced EMT. Taken together, this work identified that Rufy3 promoted cancer metastasis in CRC cells through EMT induction.