DHCR7 Promotes Liver Metastasis of Pancreatic Cancer Through PI3K-Akt Signaling Pathway

Pancreatic Cancer (PC) is associated with dismal clinical outcomes, largely due to the high prevalence of liver metastasis (LM) at diagnosis or post-resection. Despite its clinical significance, the molecular drivers of LM in PC remain poorly characterized, and few validated biomarkers or therapeutic targets are currently available. Our study identifies 7-dehydrocholesterol reductase (DHCR7), a terminal enzyme in Cholesterol biosynthesis, as significantly upregulated in PC tissues and closely correlated with LM progression. In vitro experiments demonstrated that DHCR7 enhances the proliferation, invasion, and migration ability in PC cells, and in vivo experiments demonstrated that DHCR7 promotes LM of PC. The mechanism of DHCR7 promoting LM may be mediated by elevating Cholesterol synthesis of PC cells and then activating the PI3K-Akt signaling pathway. Taken together, our findings uncover a novel molecular mechanism underlying LM in PC and highlight DHCR7 as a possible predictive biomarker or interventional target.

7‐dehydrocholesterol reductase; PI3K‐Akt; cholesterol metabolism; liver metastasis; pancreatic cancer.