ArticleScientific reports2015
The cholesterol biosynthesis enzyme oxidosqualene cyclase is a new target to impair tumour angiogenesis and metastasis dissemination.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 69 citations in OpenAlex.
- Investigating the phytotherapeutic efficacy ofFrontiers in pharmacology · 2026Article
- Crosstalk between mFrontiers in immunology · 2026Review
- Cholesterol biosynthesis as a drug-induced vulnerability in diffuse large B cell lymphoma insensitive to EZH2 inhibition.Neoplasia (New York, N.Y.) · 2025Article
- Lipid metabolic reprogramming in colorectal cancer: Insights to mechanisms and therapeutics.World journal of gastrointestinal oncology · 2025Review
- Abnormal changes in metabolites caused by mJournal of advanced research · 2025Review
- Synergistic Effects of PARP Inhibition and Cholesterol Biosynthesis Pathway Modulation.Cancer research communications · 2024Article
- Inhibition of DUSP18 impairs cholesterol biosynthesis and promotes anti-tumor immunity in colorectal cancer.Nature communications · 2024Article
- Squalene epoxidase promotes the chemoresistance of colorectal cancer via (S)-2,3-epoxysqualene-activated NF-κB.Cell communication and signaling : CCS · 2024Article
- Impact of De Novo Cholesterol Biosynthesis on the Initiation and Progression of Breast Cancer.Biomolecules · 2024Review
- Cholesterol metabolism in tumor microenvironment: cancer hallmarks and therapeutic opportunities.International journal of biological sciences · 2024Review
- Review
- Decoding Catalysis by Terpene Synthases.ACS catalysis · 2023Review
- Dysregulation of Cholesterol Homeostasis in Ovarian Cancer.Current oncology (Toronto, Ont.) · 2023Review
- Functional significance of cholesterol metabolism in cancer: from threat to treatment.Experimental & molecular medicine · 2023Review
- Lanosterol synthase loss of function decreases the malignant phenotypes of HepG2 cells by deactivating the Src/MAPK signaling pathway.Oncology letters · 2023Article
- A metabolomic and proteomic study to elucidate the molecular mechanisms of immunotherapy resistance in patients with oesophageal squamous cell carcinoma.Biomedical reports · 2023Article
- Cholesterol Biosynthesis Inhibitor RO 48-8071 Suppresses Growth of Epithelial Ovarian Cancer Cells in Vitro and In Vivo.Journal of cancer science and clinical therapeutics · 2023Article
- The role of cholesterol metabolism in tumor therapy, from bench to bed.Frontiers in pharmacology · 2023Review
- Cholesterol in colorectal cancer: an essential but tumorigenic precursor?Frontiers in oncology · 2023Review
- Terbinafine prevents colorectal cancer growth by inducing dNTP starvation and reducing immune suppression.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant cholesterol homeostasis and biosynthesis has been observed in different tumour types. This paper investigates the role of the post-squalenic enzyme of cholesterol biosynthesis, oxidosqualene cyclase (OSC), in regulating tumour angiogenesis and metastasis dissemination in mouse models of cancer. We showed that Ro 48-8071, a selective inhibitor of OSC, reduced vascular density and increased pericyte coverage, with a consequent inhibition of tumour growth in a spontaneous mouse model of pancreatic tumour (RIP-Tag2) and two metastatic mouse models of human colon carcinoma (HCT116) and pancreatic adenocarcinoma (HPAF-II). Remarkably, the inhibition of OSC hampered metastasis formation in HCT116 and HPAF-II models. Ro 48-8071 induced tumour vessel normalization and enhanced the anti-tumoral and anti-metastatic effects of 5-fluorouracil (5-FU) in HCT116 mice. Ro 48-8071 exerted a strong anti-angiogenic activity by impairing endothelial cell adhesion and migration, and by blocking vessel formation in angiogenesis assays. OSC inhibition specifically interfered with the PI3K pathway. According to in vitro results, Ro 48-8071 specifically inhibited Akt phosphorylation in both cancer cells and tumour vasculature in all treated models. Thus, our results unveil a crucial role of OSC in the regulation of cancer progression and tumour angiogenesis, and indicate Ro 48-8071 as a potential novel anti-angiogenic and anti-metastatic drug.
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