ArticleJournal of experimental & clinical cancer research : CR2019
SCP2-mediated cholesterol membrane trafficking promotes the growth of pituitary adenomas via Hedgehog signaling activation.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Cholesterol metabolism dysregulation in eyelid sebaceous gland carcinoma and its clinical significance.Indian journal of ophthalmology · 2026Article
- Comprehensive pan-cancer analysis and experimental verification of the roles of SCP2 in colon adenocarcinoma.BMC cancer · 2026Article
- Identification and Validation of Tumorigenesis Related Hub Genes in Hepatocellular Carcinoma via Integrated Bioinformatics Analysis.Iranian journal of biotechnology · 2025Article
- [Multi-omics analysis of the relationship between oxidative stress-related gene and prostate cancer].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2025Article
- Dysregulated Cholesterol Metabolism and Its Impact on the Tumour Immune Response in Colorectal Cancer.Journal of cellular and molecular medicine · 2025Review
- Aryl hydrocarbon receptor interacting protein and syndromic gene variants detected in Turkish isolated pituitary adenoma families by whole exome sequencing.Scientific reports · 2025Article
- Identification of prostate cancer potential therapeutic targets and virtual drug screening through combined Mendelian randomization study, Bayesian colocalization and molecular docking.Discover oncology · 2025Article
- Cholesterol-activated stress granules reduce the membrane localization of DRD2 and promote prolactinoma dopamine agonists resistance.Acta neuropathologica communications · 2025Article
- Targeting lipid reprogramming in the tumor microenvironment by traditional Chinese medicines as a potential cancer treatment.Heliyon · 2024Review
- Research Trends in C-Terminal Domain Nuclear Envelope Phosphatase 1.Life (Basel, Switzerland) · 2023Review
- The hidden hedgehog of the pituitary: hedgehog signaling in development, adulthood and disease of the hypothalamic-pituitary axis.Frontiers in endocrinology · 2023Review
- Solute carrier-related signature for assessing prognosis and immunity in patients with clear-cell renal cell carcinoma.Oncology research · 2023Article
- Drp1 Regulated Mitochondrial Hypofission Promotes the Invasion and Proliferation of Growth Hormone-Secreting Pituitary AdenomasFrontiers in oncology · 2022Article
- A comprehensive transcriptomic landscape of cholangiocarcinoma based on bioinformatics analysis from large cohort of patients.Scientific reports · 2021Article
- Comprehensive Analysis and Identification of Key Driver Genes for Distinguishing Between Esophageal Adenocarcinoma and Squamous Cell Carcinoma.Frontiers in cell and developmental biology · 2021Article
- The Lipid Metabolic Landscape of Cancers and New Therapeutic Perspectives.Frontiers in oncology · 2020Review
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundMetabolic reprogramming is an important characteristic of tumors. In the progression of pituitary adenomas (PA), abnormal glucose metabolism has been confirmed by us before. However, whether cholesterol metabolism is involved in the process of PA remains unclear. This study aimed to investigate whether abnormal cholesterol metabolism could affect the progression of PA.
methodsWe analyzed the expression of sterol carrier protein 2 (SCP2) in 40 surgical PA samples. In vitro experiments and xenograft models were used to assess the effects of SCP2 and cholesterol on proliferation of PA. The incidence of hypercholesterolemia between 140 PA patients and 100 heathy controls were compared.
resultsWe found an upregulation of SCP2 in PA samples, especially in tumors with high proliferation index. Forced expression of SCP2 promoted PA cell lines proliferation in vitro. Furthermore, SCP2 regulated cholesterol trafficking from cytoplasm to membrane in GH3 cells, and extracellularly treating GH3 cells and primary PA cells with methyl-β-cyclodextrin/cholesterol complex to mimic membrane cholesterol concentration enhanced cell proliferation, which suggested a proliferative effect of cholesterol. Mechanistically, cholesterol induced activation of PKA/SUFU/GLI1 signaling via smoothened receptor, which was well-known as Hedgehog signaling, resulting in inhibiting apoptosis and promoting cell cycle. Accordingly, activation of Hedgehog signaling was also confirmed in primary PA cells and surgical PA samples. In vivo, SCP2 overexpression and high cholesterol diet could promote tumor growth. Intriguingly, the incidence of hypercholesterolemia was significantly higher in PA patients than healthy controls.
conclusionsOur data indicated that dysregulated cholesterol metabolism could promote PA growth by activating Hedgehog signaling, supporting a potential tumorigenic role of cholesterol metabolism in PA progression.
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