ArticleOncogene2023
Activation of invasion by oncogenic reprogramming of cholesterol metabolism via increased NPC1 expression and macropinocytosis.
Article in Oncogene, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 18 citations in OpenAlex.
- Simvastatin reprograms lipid metabolism in B16.F10 melanoma cells to favor an early resistant phenotype.Scientific reports · 2026Article
- Organelle contact sites in cancer cells.Cell death & disease · 2026Review
- Targeting cholesterol-driven immunometabolism in cancer: from molecular circuits to clinical translation.Molecular cancer · 2026Review
- Targeting macropinocytosis for cancer therapy.Nature reviews. Cancer · 2026Review
- Comparative Analysis of Methodological Aspects of the Study of Extracellular Vesicles and Extracellular Mitochondria: From Isolation to Internalization.Current issues in molecular biology · 2026Review
- Pan-cancer analysis of cholesterol metabolism reveals the uptake as a modulator of tumor immune features and of the KRAS pathway.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Review
- Cholesterol metabolic rewiring shapes immune remodeling across hepatocarcinogenesis.Frontiers in immunology · 2026Review
- Nucleolin perturbation alters membrane lipid homeostasis.Molecular omics · 2025Article
- 27-Hydroxycholesterol in cancer development and drug resistance.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Article
- Survival strategies of cancer cells: the role of macropinocytosis in nutrient acquisition, metabolic reprogramming, and therapeutic targeting.Autophagy · 2025Review
- Article
- A comprehensive analysis identifies and validates NPC1 as a potential biomarker for prognosis in HCC.Frontiers in genetics · 2025Article
- The role of bile acid metabolism-related genes in prognosis assessment of hepatocellular carcinoma and identification of NPC1 as a biomarker.Frontiers in endocrinology · 2025Article
- Why make it if you can take it: review on extracellular cholesterol uptake and its importance in breast and ovarian cancers.Journal of experimental & clinical cancer research : CR · 2024Review
- Adaptations of membrane trafficking in cancer and tumorigenesis.Journal of cell science · 2024Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cells are dependent on cholesterol, and they possess strictly controlled cholesterol homeostasis mechanisms. These allow them to smoothly switch between cholesterol synthesis and uptake to fulfill their needs and to adapt environmental changes. Here we describe a mechanism of how cancer cells employ oncogenic growth factor signaling to promote uptake and utilization of extracellular cholesterol via Myeloid Zinc Finger 1 (MZF1)-mediated Niemann Pick C1 (NPC1) expression and upregulated macropinocytosis. Expression of p95ErbB2, highly oncogenic, standard-treatment resistant form of ErbB2 mobilizes lysosomes and activates EGFR, invasion and macropinocytosis. This is connected to a metabolic shift from cholesterol synthesis to uptake due to macropinocytosis-enabled flow of extracellular cholesterol. NPC1 increase facilitates extracellular cholesterol uptake and is necessary for the invasion of ErbB2 expressing breast cancer spheroids and ovarian cancer organoids, indicating a regulatory role for NPC1 in the process. The ability to obtain cholesterol as a byproduct of increased macropinocytosis allows cancer cells to direct the resources needed for the energy-consuming cholesterol synthesis towards other activities such as invasion. These results demonstrate that macropinocytosis is not only an alternative energy source for cancer cells but also an efficient way to provide building material, such as cholesterol, for its macromolecules and membranes.
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