C20orf27 regulates colorectal cancer growth and metastasis based on different lipid levels

Colorectal cancer (CRC) is a high-incidence malignant tumor that lacks highly effective targeted treatments currently. Epidemiology studies have revealed a direct association between high-fat diet intake and CRC. C20orf27, a key factor controlling adipose thermogenesis and glucose homeostasis, is abnormally overexpressed in CRC. However, its roles in CRC remain unknown. Therefore, our study aimed to reveal the clinical significance and biological function of C20orf27 in human CRC. Here, C20orf27 expression showed a positive correlation with patient body mass index values. Furthemore, we have demonstrated that C20orf27 promotes tumor proliferation while suppressing metastasis in CRC cells. However, under high-lipid induction conditions, C20orf27 exhibits paradoxical effects-inhibiting proliferation but enhancing metastatic potential in CRC cells. Moreover, we revealed that C20orf27 mediated CRC cell proliferation and metastasis through different signaling pathways (XBP1 or MST1) in the presence or absence of hyperlipidemia. In conclusion, our study showed the unique tumorigenic properties of C20orf27 in regulating CRC development and delineated the underlying mechanism by which it is affected by the lipid environment.