Up-regulation of FAT4 enhances the chemosensitivity of colorectal cancer cells treated by 5-FU

BACKGROUND: Colorectal cancer (CRC) has high mortality, and 5-fluorouracil (5-FU) is a common clinical chemotherapeutic drug. The current study aimed to investigate the role of FAT4 in chemosensitivity of CRC cells treated by 5-FU. METHODS: The immunohistochemistry and qRT-PCR was conducted to measure the FAT4 expression in CRC and adjacent tissues. The FAT4 expression was determined by qRT-PCR and Western blot, comparison of FAT expression between normal and several CRC cell lines was then made, so as to identify cell lines with the highest (LS174T) and the lowest (SW-620) expressions of FAT4. The effects of 5-FU stimulation at various doses on cell viability were determined by CCK-8, and the level of FAT4 was also measured. After FAT4 knockdown in LS174T or FAT4 overexpression in SW-620 with or without pretreatment of 5-FU (30 µg/mL), cell growth, colony formation, cell migration and invasion, angiogenesis were determined by flow cytometry, wound-healing, transwell assay and tube formation assay, respectively. The expression levels of epithelial-mesenchymal transition (EMT) markers were detected by qRT-PCR and Western blot. RESULTS: FAT4 was down-regulated in CRC tissues and cells, cell viability of CRC cells was decreased. The level of FAT4 was increased with the increase of 5-FU concentrations. Moreover, 5-FU stimulation increased FAT4 expression, and reduced cell proliferation, migration, invasion, angiogenesis and cell EMT process, furthermore, such effects of 5-FU stimulation could be enhanced by FAT4 overexpression but reversed by FAT4 knockdown. CONCLUSIONS: Upregulation of FAT4 could increase the sensitivity of CRC cells to 5-FU.