LAUSR

High-fat diet (HFD) leads to long-term exposure to gut microbial metabolite secondary bile acids such as deoxycholic acid (DCA) in the intestine, which is closely linked to colorectal cancer (CRC). Evidence reveals that vasculogenic mimicry (VM) is a critical event for the malignant transformation of cancer. Therefore, we aimed to investigate the crucial roles of DCA on the regulation of VM and the progression of intestinal carcinogenesis. The effects of HFD on VM formation and epithelial-mesenchymal transition (EMT) in human CRC tissues were investigated. The fecal DCA level was detected in the HFD treated-Apcmin/+ mice. Then the effects of DCA on VM formation, EMT and vascular endothelial growth factor receptor 2 (VEGFR2) signaling were evaluated in vitro and in vivo. Here we demonstrated that compared with the normal diet, HFD exacerbated VM formation and EMT in CRC patients. HFD could alter the composition of the gut microbiota and significantly increase fecal DCA level in Apcmin/+ mice. More importantly, DCA promoted tumor cell proliferation and EMT, and increased VM formation accompanied by VEGFR2 activation, which led to intestinal carcinogenesis. In addition, DCA enhanced the proliferation and migration of HCT-116 cells, and induced EMT process and vitro tube formation. Furthermore, the silence of VEGFR2 blunted DCA-induced EMT, VM formation and migration. Collectively, our results indicated that microbial metabolite DCA promoted VM formation and EMT through VEGFR2 activation, which further exacerbated intestinal carcinogenesis.