DCAF1 promotes gastric cancer progression by PI3K/AKT/mTOR pathway

Abstract

Background DCAF1 (DDB1-CUL4 associate factor 1) is a substrate receptor for two different E3 ligases, which plays an important physiological role in protein degradation and is considered to be a drug target for various cancers. However, the roles and mechanisms of DCAF1 in promoting gastric cancer (GC) progression hasn’t been fully understood yet. Methods GC samples in database and real-world were analysed to study the relationship between the expression of DCAF1 and clinicopathological characteristics and survival in GC. The mRNA and protein expressions of DCAF1 were assessed using qRT-PCR and IHC. CCK-8 and clone formation assays were employed to determine cell proliferation. Cell migration and invasion were evaluated using wound healing and transwell assays. Finally, downstream molecular mechanisms of DCAF1 affecting GC progression were explored and validated through RNA-seq and Western blot analysis. Results DCAF1 was shown to exhibit high expression in GC. Chi-square test indicated that DCAF1 was relevant with the T stage, N stage, and cTNM stage, tumor size and differentiation degree of GC. Kaplan-Meier survival curve showed that GC patients with higher DCAF1 expression had a shorter survival time. Notably, Cox regression analysis suggested that DCAF1 was an independent risk factor of GC. Functionally, DCAF1 remarkably reduced the proliferation, migration, and invasion of GC cells. Mechanistically, DCAF1 promoted GC progression through the PI3K/AKT/mTOR pathway. Conclusions Our study revealed that DCAF1 was an independent prognostic factor. Meanwhile, DCAF1 promoted GC progression by activating the PI3K/AKT/mTOR pathway, indicating that it might be a promising therapeutic target of GC.