ArticlePLoS biology2021
HMGCR inhibition stabilizes the glycolytic enzyme PKM2 to support the growth of renal cell carcinoma.
Article in PLoS biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
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- Low-Density Lipoproteins Increase Proliferation, Invasion, and Chemoresistance via an Exosome Autocrine Mechanism in MDA-MB-231 Chemoresistant Cells.Biomedicines · 2024Article
- Targeted Mevalonate Pathway and Autophagy in Antitumor Immunotherapy.Current cancer drug targets · 2024Review
- Targeting the FSH/FSHR axis in ovarian cancer: advanced treatment using nanotechnology and immunotherapy.Frontiers in endocrinology · 2024Review
- Shikonin Induces Glioma Necroptosis, Stemness Decline, and Impedes (Immuno)Proteasome Activity.Stem cells international · 2024Article
- Glycolysis-cholesterol metabolic axis in immuno-oncology microenvironment: emerging role in immune cells and immunosuppressive signaling.Cell & bioscience · 2023Review
- Liraglutide attenuates type 2 diabetes mellitus-associated non-alcoholic fatty liver disease by activating AMPK/ACC signaling and inhibiting ferroptosis.Molecular medicine (Cambridge, Mass.) · 2023Article
- MiR-122-5p regulates the mevalonate pathway by targeting p53 in non-small cell lung cancer.Cell death & disease · 2023Article
- Key events in cancer: Dysregulation of SREBPs.Frontiers in pharmacology · 2023Review
- Characterization of the microenvironment in different immune-metabolism subtypes of cervical cancer with prognostic significance.Frontiers in genetics · 2023Article
- Lipid metabolism reprogramming in head and neck cancer.Frontiers in oncology · 2023Review
- Special issue "The advance of solid tumor research in China": Multi-omics analysis based on 1311 clear cell renal cell carcinoma samples identifies a glycolysis signature associated with prognosis and treatment response.International journal of cancer · 2023Article
- Effects of oocyte vitrification on gene expression in the liver and kidney tissues of adult offspring.Journal of assisted reproduction and genetics · 2022Article
- Effects of follicle-stimulating hormone on fat metabolism and cognitive impairment in women during menopause.Frontiers in physiology · 2022Review
- Extracellular Hsp90α Supports the ePKM2-GRP78-AKT Axis to Promote Tumor Metastasis.Frontiers in oncology · 2022Article
- Dynamic transcriptome changes during osteogenic differentiation of bone marrow-derived mesenchymal stem cells isolated from chicken.Frontiers in cell and developmental biology · 2022Article
- COVID-19 inhibits spermatogenesis in the testes by inducing cellular senescence.Frontiers in genetics · 2022Article
- A Cluster of Metabolic-Related Genes Serve as Potential Prognostic Biomarkers for Renal Cell Carcinoma.Frontiers in genetics · 2022Article
- A New Prognostic Risk Signature of Eight Ferroptosis-Related Genes in the Clear Cell Renal Cell Carcinoma.Frontiers in oncology · 2021Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Renal cell carcinoma (RCC) is responsible for most cases of the kidney cancer. Previous research showed that low serum levels of cholesterol level positively correlate with poorer RCC-specific survival outcomes. However, the underlying mechanisms and functional significance of the role of cholesterol in the development of RCC remain obscure. 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) plays a pivotal role in RCC development as it is the key rate-limiting enzyme of the cholesterol biosynthetic pathway. In this study, we demonstrated that the inhibition of HMGCR could accelerate the development of RCC tumors by lactate accumulation and angiogenesis in animal models. We identified that the inhibition of HMGCR led to an increase in glycolysis via the regulated HSP90 expression levels, thus maintaining the levels of a glycolysis rate-limiting enzyme, pyruvate kinase M2 (PKM2). Based on these findings, we reversed the HMGCR inhibition-induced tumor growth acceleration in RCC xenograft mice by suppressing glycolysis. Furthermore, the coadministration of Shikonin, a potent PKM2 inhibitor, reverted the tumor development induced by the HMGCR signaling pathway.
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