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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.
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http://dx.doi.org/10.1111/cas.70185 | DOI Listing |
Cancer Sci
September 2025
Department of Pancreatic and Metabolic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
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.
View Article and Find Full Text PDFJ Exp Clin Cancer Res
June 2025
Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong First Medical University, Jinan, 250021, China.
Diffuse-type gastric cancer (DGC) accounts for approximately one-third of gastric cancer cases, but it is clinically more aggressive and associated with poorer survival prognosis compared to intestinal-type gastric cancer (IGC). Our study revealed significantly reduced ESRP1 expression in DGC patients relative to IGC counterparts, with its high expression positively correlating with DGC patient prognosis. Both in vitro and in vivo experimental models demonstrated that ESRP1 has the ability to hinder the malignant progression of DGC.
View Article and Find Full Text PDFCancer Lett
September 2025
Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA; GW Cancer Center, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA. Electronic address:
Alterations of metabolic pathways that sustain cancer cell survival often offer promising therapeutic avenues. Here, we show that enhanced de novo cholesterol biosynthesis is crucial for the survival of head and neck squamous cell carcinoma (HNSCC). Transcriptomic analysis of HNSCC tissues identified profound dysregulation in steroid and cholesterol metabolism compared to normal tissues.
View Article and Find Full Text PDFBiomolecules
May 2025
College of Animal Science and Technology, Shandong Agricultural University, 7 Panhe Street, Taian 271017, China.
The difference in chicken egg production is closely related to the efficiency of follicle selection, which is marked by granulosa cell differentiation and progesterone production with cholesterol as the substrate. The conversion of 7-dehydrocholesterol to cholesterol catalyzed by 7-Dehydrocholesterol reductase (DHCR7) is the rate-limiting step in cholesterol synthesis. Our previous study revealed that estrogen enhanced the mRNA expression of three transcript variants (T1, T3, and T4) in a dose-dependent manner in the granulosa cells of chicken pre-hierarchical follicles (Pre-GCs).
View Article and Find Full Text PDFNutrition
September 2025
Department of Clinical and Social Nutrition, Research and Study Group on Nutrition and Public Health (GPENSC), School of Nutrition, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.
Background: The association between vitamin D and depression is controversial, mainly because of genetic differences and confounding factors.
Objective: To evaluate the association between vitamin D and depressive symptoms, considering the influence of genetic variations, skin color, and lifestyle.
Methods: This population-based cross-sectional study was conducted during the COVID-19 pandemic.