ArticleCancer discovery2013
Targeting C4-demethylating genes in the cholesterol pathway sensitizes cancer cells to EGF receptor inhibitors via increased EGF receptor degradation.
Article in Cancer discovery, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Chemical Inhibition of Sterol Biosynthesis.Biomolecules · 2024Pooled it
- Clustering of host N-glycans by the microneme MIC1/4/6 complex licenses Toxoplasma rhoptry discharge.The EMBO journal · 2026Article
- The NSDHL/c-Myc/PKM2 Axis Drives Glycolytic Reprogramming and Tumor Growth in Multiple Myeloma.International journal of molecular sciences · 2026Article
- MSMO1 promotes chemotherapy resistance through modulation of T-MAS metabolism via PERK/elF2α/ATF4/CHOP pathway.iScience · 2026Article
- METTL16-mediated mJournal of experimental & clinical cancer research : CR · 2026Article
- Integrated Bioinformatics Analysis Revealing that the NSDHL Gene Might Be Associated with the Progression of Western HFD/SW-Induced Hepatocellular CarcinomaEndocrine, metabolic & immune disorders drug targets · 2026Article
- Proteomic Profiling Informs Mechanisms of Esophageal Adenocarcinoma Inhibition by Cranberry Proanthocyanidins.Molecular nutrition & food research · 2025Article
- CYP51A1 in health and disease: from sterol metabolism to regulated cell death.Cell death discovery · 2025Review
- Exploring the genetic causal inference between plasma lipidome and lung carcinoma: a bidirectional mendelian randomization study.Discover oncology · 2025Article
- Cholesterol-activated stress granules reduce the membrane localization of DRD2 and promote prolactinoma dopamine agonists resistance.Acta neuropathologica communications · 2025Article
- Up-regulation of MSMO1 was associated with poor survival in cervical cancer.Translational cancer research · 2024Article
- The cholesterol biosynthesis enzyme FAXDC2 couples Wnt/β-catenin to RTK/MAPK signaling.The Journal of clinical investigation · 2024Article
- Evaluation of Antifungal Selective Toxicity UsingJournal of fungi (Basel, Switzerland) · 2023Article
- Arf5-mediated regulation of mTORC1 at the plasma membrane.Molecular biology of the cell · 2023Article
- Lipids in cancer: a global view of the contribution of lipid pathways to metastatic formation and treatment resistance.Oncogenesis · 2022Review
- CPSF1 positively regulates NSDHL by alternative polyadenylation and promotes gastric cancer progression.American journal of cancer research · 2022Article
- Down-regulation of MSMO1 promotes the development and progression of pancreatic cancer.Journal of Cancer · 2022Article
- Intracellular Cholesterol Synthesis and Transport.Frontiers in cell and developmental biology · 2022Review
- [Steroidogenic acute regulatory protein-related lipid transfer 4 (StarD4) promotes breast cancer cell proliferation and its mechanism].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2021Article
- Plasma extracellular vesicle long RNA profiles in the diagnosis and prediction of treatment response for breast cancer.NPJ breast cancer · 2021Article
Corrections and comments
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Authors and funding
24 authors at 6 institutions in 1 country.
Funding
Abstract
unlabelledPersistent signaling by the oncogenic EGF receptor (EGFR) is a major source of cancer resistance to EGFR targeting. We established that inactivation of 2 sterol biosynthesis pathway genes, SC4MOL (sterol C4-methyl oxidase-like) and its partner, NSDHL (NADP-dependent steroid dehydrogenase-like), sensitized tumor cells to EGFR inhibitors. Bioinformatics modeling of interactions for the sterol pathway genes in eukaryotes allowed us to hypothesize and then extensively validate an unexpected role for SC4MOL and NSDHL in controlling the signaling, vesicular trafficking, and degradation of EGFR and its dimerization partners, ERBB2 and ERBB3. Metabolic block upstream of SC4MOL with ketoconazole or CYP51A1 siRNA rescued cancer cell viability and EGFR degradation. Inactivation of SC4MOL markedly sensitized A431 xenografts to cetuximab, a therapeutic anti-EGFR antibody. Analysis of Nsdhl-deficient Bpa(1H/+) mice confirmed dramatic and selective loss of internalized platelet-derived growth factor receptor in fibroblasts, and reduced activation of EGFR and its effectors in regions of skin lacking NSDHL. SIGNIFICANCE: This work identifies a critical role for SC4MOL and NSDHL in the regulation of EGFR signaling and endocytic trafficking and suggests novel strategies to increase the potency of EGFR antagonists in tumors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.