Oncogene StarD4 had the function of promoting proliferation and metastasis of triple-negative breast cancer (TNBC), but its clinical value and molecular mechanism are unknown. This paper found that StarD4 was highly expressed in cancer tissues of TNBC patients, and higher expression level of StarD4 in TNBC patient resulted in poorer prognosis. Based on transcriptomics of MDA-MB-231 cell model, the results of bioinformatics analysis showed that down-regulated expression level of StarD4 led to overall downregulation of cholesterol-relative genes and significant enrichment of cancer mechanism and pathway. Further analysis and investigation verified that StarD4 might cross-promote the protein stability of receptor ITGA5 through the cholesterol pathway to enhance TNBC progression, which provides guidance for clinical application of TNBC diagnosis and treatment.
ObjectiveTo summarize the remodeling of cholesterol metabolism in the occurrence and progression of pancreatic ductal adenocarcinoma (PDAC), and to review the research progress on targeted cholesterol metabolism in the treatment of PDAC. MethodRelevant literatures on cholesterol metabolism in the occurrence, development, and diagnosis and treatment of PDAC in recent years were searched and reviewed. ResultsMetabolites of PDAC tumor cells affected the expression of oncogenes or tumor suppressor genes. Signaling regulation within tumor cells affects cholesterol metabolism, characterized by increased de novo cholesterol synthesis and esterification, and reduced efflux. Tumor cells also regulated tumor immune microenvironment or tumor stroma formation through cholesterol metabolism. Inhibiting cholesterol metabolism could suppress the proliferation, invasion and migration of PDAC tumor cells, and combination therapy targeting cholesterol metabolism had a synergistic anti-PDAC effect. ConclusionsRemodeling of cholesterol metabolism occurs in both PDAC tumor cells and the tumor microenvironment, and is closely related to the occurrence, development, invasion, metastasis, and treatment response of PDAC. Targeting cholesterol metabolism or combined application with chemotherapy drugs can have anticancer effects. However, more research is needed to support the translation of cholesterol metabolism regulation into clinical treatment applications.