ArticleBreast cancer research : BCR2020
Progesterone receptor membrane component 1 regulates lipid homeostasis and drives oncogenic signaling resulting in breast cancer progression.
Article in Breast cancer research : BCR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.
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33 citing papers in PubMed, 55 citations in OpenAlex.
- Lipid metabolism reprogramming: key mechanism of breast cancer endocrine therapy resistance.Frontiers in oncology · 2026Review
- Sonication-assisted protein extraction improves proteomic detection of membrane-bound and DNA-binding proteins from tumor tissues.Nature protocols · 2025Review
- Transformer Decoder Learns from a Pretrained Protein Language Model to Generate Ligands with High Affinity.Journal of chemical information and modeling · 2025Article
- Ternary Complex Components Responsible for Rapid LDL Internalization as Biomarkers for Breast Cancer Associated with Proliferation and Early Recurrence.Cancer research communications · 2025Article
- Liver-specific gene PGRMC1 blocks c-Myc-induced hepatocarcinogenesis through ER stress-independent PERK activation.Nature communications · 2025Article
- Identification of FDFT1 and PGRMC1 as New Biomarkers in Nonalcoholic Steatohepatitis (NASH)-Related Hepatocellular Carcinoma by Deep Learning.Journal of hepatocellular carcinoma · 2025Article
- Roles for PMP22 in Schwann cell cholesterol homeostasis in health and disease.Biochemical Society transactions · 2024Review
- Pleiotropy of Progesterone Receptor Membrane Component 1 in Modulation of Cytochrome P450 Activity.Journal of xenobiotics · 2024Review
- Article
- Clinical Importance of PGRMC1 in Hormone Responsive Breast Cancer.Breast care (Basel, Switzerland) · 2023Review
- PGRMC1: An enigmatic heme-binding protein.Pharmacology & therapeutics · 2023Review
- Novel lipometabolism biomarker for chemotherapy and immunotherapy response in breast cancer.BMC cancer · 2022Article
- Pleiotropic Actions of PGRMC Proteins in Cancer.Endocrinology · 2022Review
- Review
- Article
- Article
- Solving the Puzzle: What Is the Role of Progestogens in Neovascularization?Biomolecules · 2021Review
- Article
- PGRMC1-dependent lipophagy promotes ferroptosis in paclitaxel-tolerant persister cancer cells.Journal of experimental & clinical cancer research : CR · 2021Article
- Review
Corrections and comments
- Erratum issued
Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundPGRMC1 (progesterone receptor membrane component 1) is a highly conserved heme binding protein, which is overexpressed especially in hormone receptor-positive breast cancer and plays an important role in breast carcinogenesis. Nevertheless, little is known about the mechanisms by which PGRMC1 drives tumor progression. The aim of our study was to investigate the involvement of PGRMC1 in cholesterol metabolism to detect new mechanisms by which PGRMC1 can increase lipid metabolism and alter cancer-related signaling pathways leading to breast cancer progression.
methodsThe effect of PGRMC1 overexpression and silencing on cellular proliferation was examined in vitro and in a xenograft mouse model. Next, we investigated the interaction of PGRMC1 with enzymes involved in the cholesterol synthesis pathway such as CYP51, FDFT1, and SCD1. Further, the impact of PGRMC1 expression on lipid levels and expression of enzymes involved in lipid homeostasis was examined. Additionally, we assessed the role of PGRMC1 in key cancer-related signaling pathways including EGFR/HER2 and ERα signaling.
resultsOverexpression of PGRMC1 resulted in significantly enhanced proliferation. PGRMC1 interacted with key enzymes of the cholesterol synthesis pathway, alters the expression of proteins, and results in increased lipid levels. PGRMC1 also influenced lipid raft formation leading to altered expression of growth receptors in membranes of breast cancer cells. Analysis of activation of proteins revealed facilitated ERα and EGFR activation and downstream signaling dependent on PGRMC1 overexpression in hormone receptor-positive breast cancer cells. Depletion of cholesterol and fatty acids induced by statins reversed this growth benefit.
conclusionPGRMC1 may mediate proliferation and progression of breast cancer cells potentially by altering lipid metabolism and by activating key oncogenic signaling pathways, such as ERα expression and activation, as well as EGFR signaling. Our present study underlines the potential of PGRMC1 as a target for anti-cancer therapy.
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