Affinage

HMGCS1

Hydroxymethylglutaryl-CoA synthase, cytoplasmic · UniProt Q01581

Length
520 aa
Mass
57.3 kDa
Annotated
2026-06-10
50 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HMGCS1 is the cytosolic enzyme catalyzing the condensation step that generates HMG-CoA, committing acetyl units to the mevalonate/cholesterol biosynthesis pathway, and its activity governs cellular cholesterol and isoprenoid supply across development, metabolism, and cancer (PMID:35671633, PMID:39531736). Catalysis depends on an active-site cysteine, Cys129, which is the target of irreversible covalent inhibition by epoxide-bearing natural-product metabolites of ursolic acid and ligustilide, and the enzyme is also blocked selectively by the covalent inhibitor hymeglusin (PMID:35671633, PMID:37579692, PMID:40631324). Biallelic hypomorphic missense variants that reduce HMGCS1 enzymatic activity and thermal stability while sparing dimerization cause rigid spine syndrome in humans, with the zebrafish phenotype rescued by mevalonic acid supplementation, establishing HMGCS1 as a disease gene acting through partial loss of mevalonate pathway output (PMID:39531736). Beyond canonical cytosolic cholesterol synthesis, HMGCS1 displays compartment-specific functions: it translocates to the nucleus to directly bind and activate the Oct4 and SOX2 promoters and engage the ER-stress transducer PERK, and a mitochondrial pool associates with the mtDNA D-loop to stabilize binding of the core transcription machinery POLRMT, TFAM, and TFB2M, sustaining respiratory subunit transcription and respiration (PMID:32349352, PMID:36328117, PMID:41545954). HMGCS1-derived cholesterol mediates plasma-membrane repair by directly binding CHMP4B to promote its membrane localization, enabling tumor cells to evade perforin-mediated cytotoxic lymphocyte killing (PMID:42248910). HMGCS1 expression is tightly controlled: transcriptionally activated by SREBF2, NRF2, STAT1, GATA1, ERRα, and c-Jun and repressed or promoted in a context-dependent manner by KLF13, with TET2-driven promoter demethylation as an additional input; its mRNA is stabilized by IGF2BP2- and RPL6-containing complexes and degraded via METTL3/YTHDF2 m6A turnover; and its protein is deacetylated by SIRT1 and stabilized when CSN6 antagonizes SPOP-mediated ubiquitination (PMID:21701047, PMID:32523679, PMID:31554653, PMID:38308184, PMID:36348011, PMID:36356901, PMID:36381108, PMID:35945406, PMID:40839015, PMID:42248910, PMID:36734275, PMID:40650669). Through these inputs HMGCS1 sustains mevalonate-dependent prenylation, ERK/MAPK signaling, and downstream oncogenic effectors such as YAP1 and HIF-1α to drive proliferation, invasion, and therapy resistance in multiple cancers (PMID:31554653, PMID:38308184, PMID:36348011, PMID:38994525, PMID:40650669).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2011 Medium

    Established that HMGCS1 is not only a metabolic enzyme but a post-translationally regulated protein, identifying it as a cytoplasmic SIRT1 deacetylation substrate parallel to the mitochondrial HMGCS2/SIRT3 pair.

    Evidence deacetylation assay with substrate-homology analysis

    PMID:21701047

    Open questions at the time
    • Functional consequence of HMGCS1 acetylation/deacetylation on enzyme activity not defined
    • Specific acetylated lysines not mapped
  2. 2017 Medium

    Linked HMGCS1 mevalonate output to organismal phenotype, showing its loss disrupts cranial neural crest differentiation via isoprenoid (not solely cholesterol) synthesis, while also tying it to cancer cell viability through autocrine/paracrine pathway activity.

    Evidence zebrafish hmgcs1 loss-of-function with pharmacological dissection; shRNA knockdown and overexpression in prostate cancer cells

    PMID:28686747 PMID:29163687

    Open questions at the time
    • Molecular targets of isoprenoid signaling in neural crest unresolved
    • Shh pathway changes appeared only after morphological defects, leaving causality unclear
  3. 2019 Medium

    Revealed a mevalonate-independent signaling role and identified the first transcriptional regulators, showing HMGCS1 enhances ERK phosphorylation and EGF-driven proliferation while SREBF2 and GATA1-dependent isoprenoids feed into HMGCS1/GATA1-controlled erythroid differentiation.

    Evidence knockdown with pERK readout and pathway-independence pharmacology; zebrafish missense mutant with gata1a expression and isoprenoid epistasis

    PMID:30987969 PMID:31554653

    Open questions at the time
    • Mechanism by which HMGCS1 enhances ERK independently of catalysis unknown
    • Direct molecular link between isoprenoids and gata1a not identified
  4. 2020 Medium

    Defined a moonlighting nuclear function and context-dependent transcriptional control, demonstrating nuclear HMGCS1 directly activates pluripotency promoters and binds PERK, while KLF13 represses HMGCS1 to limit cholesterol synthesis and proliferation.

    Evidence ChIP, Co-IP, nuclear fractionation, and pathway-blockade in gastric cancer; ChIP-qPCR and luciferase reporter with KLF13 manipulation in CRC

    PMID:32349352 PMID:32523679

    Open questions at the time
    • Signal/mechanism driving HMGCS1 nuclear translocation unresolved
    • Whether nuclear DNA binding is direct or via cofactors not established
  5. 2021 Medium

    Expanded the regulatory network and stress-protective role, identifying GATA1 as a direct activator and showing HMGCS1 protects mitochondria/ER under stress and engages in Gal-7 positive feedback via a defined interaction at Phe26.

    Evidence promoter binding and ER-stress/UPR assays in AML; yeast two-hybrid, Biacore SPR, Co-IP, and F26 mutagenesis in keratinocytes

    PMID:33601148 PMID:34454908

    Open questions at the time
    • Whether Gal-7 binding alters HMGCS1 catalysis directly is not shown
    • Mechanism of ER/mitochondrial protection beyond UPR upregulation not defined
  6. 2022 High

    Pinpointed the catalytic active site and mapped multilayer expression control, showing Cys129 is the irreversibly inhibited residue and that NRF2, STAT1, TET2 demethylation, and KLF13 all converge on HMGCS1 transcription, with distinct cytosolic versus mitochondrial functional compartments emerging.

    Evidence covalent-binding chemical biology (ursolic acid metabolite, Cys129); transcription factor reporter/knockdown studies; TET2 promoter demethylation with GGPP and GTPase localization rescue; subcellular fractionation with compartment-specific functional assays

    PMID:32523679 PMID:35671633 PMID:35945406 PMID:36328117 PMID:36348011 PMID:36356901 PMID:36381108

    Open questions at the time
    • Opposing KLF13 effects in CRC versus HCC indicate unresolved context dependence
    • Mechanism targeting HMGCS1 to mitochondria not defined at this stage
  7. 2023 Medium

    Extended HMGCS1 into invasion programs and mRNA-stability control, showing ERRα physically interacts with HMGCS1 to promote invadopodia/EMT and that a second covalent ligand (ligustilide metabolite) confirms Cys129, while VIM-AS1/IGF2BP2 stabilizes HMGCS1 mRNA.

    Evidence Co-IP and invasion assays with ERRα; covalent Cys129 binding assay; RNA pulldown/RIP and mRNA-stability/rescue experiments

    PMID:36734275 PMID:36835419 PMID:37579692

    Open questions at the time
    • Whether ERRα binding affects HMGCS1 catalysis or localization unclear
    • Direct versus scaffolded IGF2BP2 binding to HMGCS1 transcript not fully resolved
  8. 2024 Medium

    Consolidated post-translational and signaling axes, showing CSN6 stabilizes HMGCS1 against SPOP-mediated degradation to activate YAP1, that ACSS2 physically partners with HMGCS1 upstream of PI3K/AKT/mTOR, that m6A (METTL3/YTHDF2) controls HMGCS1 mRNA fate, and that HMGCS1 drives AML chemoresistance through MAPK.

    Evidence Co-IP, ubiquitination, and YAP1 assays; Co-IP and rescue epistasis with ACSS2; MeRIP-qPCR with writer/reader manipulation; MEK-inhibitor epistasis with genetic manipulation

    PMID:38263056 PMID:38308184 PMID:38994525 PMID:40839015

    Open questions at the time
    • Whether ACSS2-HMGCS1 binding is metabolic channeling or signaling scaffolding not resolved
    • How HMGCS1 mechanistically activates YAP1 and MAPK not fully defined
  9. 2025 High

    Delivered the strongest mechanistic and disease-level evidence: a mitochondrial HMGCS1 pool stabilizes the mtDNA transcription machinery at the D-loop; cholesterol made by HMGCS1 directly binds CHMP4B to drive membrane repair and immune evasion; and biallelic hypomorphic variants cause rigid spine syndrome rescued by mevalonic acid.

    Evidence D-loop ChIP and Co-IP with POLRMT/TFAM/TFB2M plus respiration assays; functional enzyme screen with cholesterol-CHMP4B binding and perforin/NK/CAR-T killing assays plus c-Jun ChIP; recombinant mutant enzymology/stability with zebrafish mevalonic-acid rescue and exome sequencing

    PMID:39531736 PMID:41545954 PMID:42248910

    Open questions at the time
    • How HMGCS1 is imported into mitochondria and nucleus is unresolved
    • Whether mitochondrial/nuclear functions require catalytic activity not fully separated from metabolic effects
  10. 2025 Medium

    Refined therapeutic targeting and downstream metabolic consequences, validating hymeglusin as a selective covalent HMGCS1 inhibitor whose effects mirror HMGCR loss, linking HMGCS1 to HIF-1α stabilization, GPX4/selenocysteine-tRNA-dependent ferroptosis, and steroidogenesis.

    Evidence activity-based protein profiling and chemical proteomics (preprint); RPL6 3'UTR binding with HIF-1α ubiquitination assays; cerulenin enzymatic inhibition with selenocysteine-tRNA/GPX4 analysis; transcriptomics/metabolomics with HMGCS1 inhibition in Sertoli cells

    PMID:40413863 PMID:40631324 PMID:40650669 PMID:40848803

    Open questions at the time
    • Sertoli-cell steroidogenesis link is correlative and from a non-human model
    • Selectivity of cerulenin between FASN and HMGCS1 in cells not fully separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • The signals and import machinery that direct HMGCS1 to the nucleus and mitochondria, and whether its moonlighting transcriptional and membrane-repair roles depend on catalysis versus protein scaffolding, remain undefined.
  • No structural model of compartment-specific HMGCS1 complexes
  • Catalysis-dependent versus -independent moonlighting functions not cleanly separated
  • Mechanism of regulated subcellular targeting unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0003677 DNA binding 2 GO:0016787 hydrolase activity 2
Localization
GO:0005634 nucleus 2 GO:0005739 mitochondrion 2 GO:0005829 cytosol 2 GO:0000228 nuclear chromosome 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-1643685 Disease 1
Partners
ACSS2CHMP4BERRΑLGALS7PERKPOLRMTTFAMTFB2M

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 SIRT1 deacetylates HMGCS1 in the cytoplasm, establishing HMGCS1 as a substrate for the cytoplasmic deacetylase SIRT1 (analogous to the SIRT3/HMGCS2 pair in mitochondria). Deacetylation assay; evolutionary/substrate homology analysis Aging Medium 21701047
2017 Knockdown of HMGCS1 by shRNA significantly reduces prostate cancer cell viability, and exogenous overexpression of HMGCS1 in prostate cancer or stromal cells stimulates cancer cell growth, demonstrating a functional role via autocrine/paracrine mevalonate pathway activity. shRNA knockdown, overexpression, cell viability assays Oncology letters Medium 29163687
2020 KLF13 transcriptionally inhibits HMGCS1 expression by binding to the HMGCS1 promoter, thereby suppressing HMGCS1-mediated cholesterol biosynthesis and reducing CRC cell proliferation. ChIP-qPCR, luciferase reporter assay, KLF13 overexpression/knockdown with cholesterol measurement Cell & bioscience Medium 32523679
2020 HMGCS1 promotes gastric cancer progression through both metabolic (mevalonate pathway) and nonmetabolic functions: under serum deprivation, HMGCS1 translocates to the nucleus, directly binds to and activates Oct4 and SOX-2 promoters, and interacts with the ER stress transducer PERK to enhance the integrated stress response. ChIP assay, Co-IP, promoter binding assays, statin/dipyridamole pharmacological blockade, nuclear fractionation Cancers Medium 32349352
2019 HMGCS1 enhances ERK phosphorylation (pERK) activity independently of the mevalonate pathway in colon cancer cells, and its suppression completely abolishes EGF-induced proliferation; SREBF2 is identified as a transcription factor regulating HMGCS1 expression. HMGCS1 knockdown, EGF stimulation, pERK measurement, SREBF2 transcription factor analysis Molecular cancer therapeutics Medium 31554653
2021 GATA1 is identified as a direct upstream transcriptional regulator of HMGCS1, binding to the HMGCS1 promoter in AML cells; HMGCS1 protects mitochondria and ER from damage under ER stress and upregulates UPR downstream components, conferring chemotherapy resistance. Promoter binding assay, Tunicamycin ER stress treatment, mitochondrial analysis, UPR component measurement Biomedicine & pharmacotherapy Medium 33601148
2022 Ursolic acid (UA) metabolite epoxy-modified UA irreversibly binds to the thiol of Cys-129 in HMGCS1, inhibiting its catalytic activity and reducing cholesterol biosynthesis precursor generation in vivo. Molecular docking, in-gel fluorescence scan, thermal shift assay, targeted metabolomics, fluorescence colocalization Phytomedicine High 35671633
2017 Loss-of-function mutation of zebrafish hmgcs1 (encoding the first enzyme of the cholesterol synthesis pathway) causes craniofacial abnormalities via defects in cranial neural crest cell differentiation; isoprenoid synthesis (independent of cholesterol) was also found to have a novel role in facial development; Shh signaling was unaffected at early stages but gli1 expression was reduced at 4 dpf after morphological defects appeared. Zebrafish hmgcs1 loss-of-function mutation, pharmacological pathway inhibition, Shh pathway gene expression analysis PloS one Medium 28686747
2019 Mutation of zebrafish hmgcs1 decreases mature red blood cell numbers coinciding with reduced gata1a expression; isoprenoid synthesis (not cholesterol alone) is required for gata1a expression, establishing a novel role for HMGCS1-dependent isoprenoids as upstream regulators of GATA1 and RBC differentiation. Zebrafish hmgcs1 missense mutant analysis, RBC counting, gata1a expression, pharmacological inhibition of cholesterol/isoprenoid synthesis Blood advances Medium 30987969
2022 HMGCS1 shows a compartmentalized distribution in nuclei, cytosol, and mitochondria of cervical cancer cells; cytosolic HMGCS1 regulates radiosensitivity via cholesterol metabolism, while mitochondrial HMGCS1 controls mitochondrial gene expression and sustains mitochondrial function. Subcellular fractionation, loss-of-function with radiosensitivity assay, mitochondrial gene expression analysis Cellular signalling Medium 36328117
2024 CSN6 stabilizes HMGCS1 protein by antagonizing SPOP ubiquitin ligase-mediated degradation; stabilized HMGCS1 in turn activates YAP1 to promote hepatocellular carcinoma tumor growth. Co-IP, ubiquitination assay, HMGCS1 protein stability analysis, YAP1 activity measurement, orthotopic liver cancer models Advanced science Medium 38308184
2022 TET2 directly regulates HMGCS1 expression by catalyzing DNA demethylation on the HMGCS1 promoter region; TET2 deficiency leads to downregulation of HMGCS1 and the mevalonate pathway, sensitizing cells to statin-induced apoptosis via decreased geranylgeranyl diphosphate (GGPP) and impaired membrane localization of small GTPases. TET2 knockout, HMGCS1 promoter demethylation analysis, GGPP measurement, small GTPase membrane localization assay, HMGCS1 overexpression rescue Oncogene Medium 36348011
2022 Metformin downregulates HMGCS1 expression through inhibition of the transcription factor NRF2 (nuclear factor E2-related factor 2), establishing NRF2 as an upstream transcriptional activator of HMGCS1. HMGCS1 expression analysis after metformin treatment, NRF2 inhibition/knockdown with reporter assays, in vitro and in vivo tumor models The Journal of biological chemistry Medium 36356901
2021 Gal-7 (galectin-7) directly interacts with HMGCS1 at phenylalanine 26 of HMGCS1; this interaction upregulates HMGCS1 expression in keratinocytes, increasing cellular cholesterol, and the two proteins engage in positive feedback regulation. Yeast two-hybrid, in vitro β-galactosidase assay, Biacore surface plasmon resonance, immunoprecipitation, F26 mutagenesis peptide inhibition The Journal of investigative dermatology High 34454908
2023 Ligustilide (Lig) metabolic intermediate 6,7-epoxyligustilide irreversibly binds to Cys129 of HMGCS1 via covalent modification, inhibiting HMGCS1 catalytic activity and reducing cholesterol synthesis to ameliorate dyslipidemia. Chemical biological analysis, molecular docking, covalent binding assay targeting Cys129, in vivo hyperlipidemia model Biomedicine & pharmacotherapy High 37579692
2022 KLF13 transcriptionally promotes HMGCS1 expression and cholesterol biosynthesis in hepatocellular carcinoma, as shown by dual-luciferase reporter assay and ChIP-seq confirming KLF13 binding to the HMGCS1 promoter, with KLF13 knockdown inhibiting cholesterol and HCC cell growth. Dual-luciferase reporter assay, ChIP-seq, KLF13 overexpression/knockdown, cholesterol measurement Journal of clinical and translational hepatology Medium 36381108
2024 ACSS2 physically interacts with HMGCS1 (confirmed by Co-IP) in pancreatic neuroendocrine neoplasms; HMGCS1 can reverse the lipid metabolism reprogramming and PI3K/AKT/mTOR pathway effects caused by ACSS2 knockdown, placing HMGCS1 downstream of ACSS2 in this signaling axis. Co-immunoprecipitation, HMGCS1 overexpression rescue of ACSS2 knockdown, PI3K/AKT/mTOR pathway analysis, nude mouse xenografts Journal of translational medicine Medium 38263056
2022 STAT1 is a transcriptional activator of HMGCS1; miR-379-5p inhibits STAT1 expression thereby suppressing STAT1-driven HMGCS1 transcription and reducing free cholesterol accumulation in hepatocytes. Luciferase assay, mass spectrometry, STAT1 knockdown with HMGCS1 expression measurement, miR-379-5p overexpression in db/db mice Molecular biomedicine Medium 35945406
2024 HMGCS1 is subject to m6A RNA methylation by METTL3; YTHDF2 recognizes and degrades m6A-modified HMGCS1 mRNA, thereby reducing HMGCS1 protein levels and promoting ferroptosis in retinal ganglion cells under glutamate excitotoxicity. MeRIP-qPCR, siRNA knockdown of YTHDF2/HMGCS1, HMGCS1 lentiviral overexpression, ferroptosis markers, METTL3 inhibitor (STM2457), Western blot International journal of surgery Medium 40839015
2023 ERRα directly interacts with HMGCS1 (confirmed by Co-IP) in endometrial cancer cells to regulate intracellular cholesterol metabolism and promote invadopodia formation, thereby enhancing cancer invasion and metastasis via the epithelial-mesenchymal transition pathway. Co-immunoprecipitation, ERRα/HMGCS1 loss-of-function and gain-of-function assays, cholesterol measurement, invasion assays, simvastatin treatment International journal of molecular sciences Medium 36835419
2025 Biallelic missense variants in HMGCS1 cause rigid spine syndrome in humans; four tested variants (S447P, Q29L, M70T, C268S) show reduced HMGCS1 enzymatic activity and/or thermal stability while maintaining dimerization; mevalonic acid supplementation rescues the zebrafish mutant phenotype, establishing HMGCS1 as a disease gene acting through hypomorphic reduction of mevalonate pathway function. Recombinant protein enzymatic activity assay, thermal stability assay, dimerization assay, zebrafish rescue with HMGCS1 mRNA and mevalonic acid supplementation, exome/genome sequencing Brain High 39531736
2024 HMGCS1 knockdown in AML cells suppresses MAPK pathway activity, while HMGCS1 overexpression enhances it; MEK1 inhibitor U0126 offsets HMGCS1 overexpression effects, establishing that HMGCS1 promotes AML chemoresistance through the MAPK pathway. HMGCS1 knockout/overexpression, MAPK pathway phosphorylation analysis, MEK inhibitor epistasis, hymeglusin pharmacological inhibition Blood science Medium 38994525
2025 Mitochondrial HMGCS1 associates with the D-loop region of mitochondrial DNA and is required for stable binding of core mitochondrial transcription machinery components (POLRMT, TFAM, TFB2M) to mtDNA, thereby regulating mitochondrial respiratory complex subunit transcription and mitochondrial respiratory capacity in cisplatin-resistant cervical cancer cells. Mitochondrial targeting construct, D-loop ChIP, Co-IP with POLRMT/TFAM/TFB2M, mitochondrial transcription and respiration assays, HMGCS1 inhibition/depletion with cisplatin sensitivity rescue BMC molecular and cell biology High 41545954
2025 HMGCS1 drives cholesterol-dependent plasma membrane repair after perforin-induced damage; cholesterol synthesized by HMGCS1 directly binds CHMP4B to enhance its plasma membrane localization, facilitating membrane repair and enabling tumor immune evasion; c-Jun transcriptionally upregulates HMGCS1 expression in response to oncogenic activation, cytokines, and hypoxia. Functional metabolic enzyme screen (111 enzymes), cholesterol-CHMP4B binding assay, HMGCS1 knockout with perforin/NK/CAR-T killing assays, c-Jun ChIP, PM repair assay Nature communications High 42248910
2025 Activity-based chemical probes confirmed Hymeglusin as a selective covalent inhibitor of HMGCS1; inhibiting HMGCS1 causes proteome changes nearly identical to those caused by HMGCR inhibition or HMGCS1 degradation; simultaneous targeting of HMGCS1 and HMGCR suppresses growth of statin-resistant cancer cells and xenografts. Activity-based protein profiling, chemical proteomics, proteome-wide selectivity assay, xenograft tumor models, serum stability assay bioRxivpreprint Medium 40631324
2023 VIM-AS1 lncRNA promotes HMGCS1 mRNA stability through formation of a VIM-AS1/IGF2BP2/HMGCS1 RNA-protein complex, increasing HMGCS1 protein levels and promoting prostate cancer cell proliferation and enzalutamide resistance; HMGCS1 knockdown rescues VIM-AS1 overexpression-induced proliferation and resistance. RNA pulldown, RNA immunoprecipitation, RNA sequencing, HMGCS1 mRNA stability assay, rescue experiments International journal of oncology Medium 36734275
2025 RPL6 directly binds the HMGCS1 mRNA 3'UTR (confirmed by RIP/binding assay), increasing HMGCS1 mRNA stability and protein expression; elevated HMGCS1-derived cholesterol inhibits ubiquitin-dependent HIF-1α degradation, activating HIF-1α signaling to promote HCC metastasis. HMGCS1 mRNA 3'UTR binding assay, mRNA stability analysis, cholesterol measurement, HIF-1α ubiquitination assay, in vitro and in vivo metastasis models Advanced science Medium 40650669
2025 In porcine Sertoli cells, HMGCS1 positively regulates dehydroepiandrosterone (DHEA) levels; melatonin treatment reduces HMGCS1 expression and estradiol levels, and direct HMGCS1 inhibition also reduces estradiol, establishing an HMGCS1-estradiol pathway in Sertoli cell steroidogenesis. Integrated transcriptomics/metabolomics, HMGCS1 inhibition with DHEA/estradiol measurement, RT-qPCR, Western blot Theriogenology Low 40413863
2025 Cerulenin dually targets and inhibits both FASN and HMGCS1 enzymatic activity; HMGCS1 inhibition by cerulenin disrupts the mevalonate pathway, leading to impaired selenocysteine tRNA maturation and subsequent suppression of GPX4 protein synthesis, enhancing tumor cell sensitivity to ferroptosis inducers. Enzymatic activity assay, mevalonate pathway metabolite analysis, selenocysteine tRNA and GPX4 synthesis measurement, xenograft tumor model Cancer letters Medium 40848803

Source papers

Stage 0 corpus · 50 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 SIRT1 and SIRT3 deacetylate homologous substrates: AceCS1,2 and HMGCS1,2. Aging 90 21701047
2017 Stromal regulation of prostate cancer cell growth by mevalonate pathway enzymes HMGCS1 and HMGCR. Oncology letters 61 29163687
2020 Sevoflurane suppresses cell viability and invasion and promotes cell apoptosis in colon cancer by modulating exosome‑mediated circ‑HMGCS1 via the miR‑34a‑5p/SGPP1 axis. Oncology reports 49 33125091
2020 KLF13 suppresses the proliferation and growth of colorectal cancer cells through transcriptionally inhibiting HMGCS1-mediated cholesterol biosynthesis. Cell & bioscience 43 32523679
2024 Hypoxia upregulating ACSS2 enhances lipid metabolism reprogramming through HMGCS1 mediated PI3K/AKT/mTOR pathway to promote the progression of pancreatic neuroendocrine neoplasms. Journal of translational medicine 41 38263056
2020 The STAT3-miR-223-TGFBR3/HMGCS1 axis modulates the progression of cervical carcinoma. Molecular oncology 39 32491253
2020 Mevalonate Pathway Enzyme HMGCS1 Contributes to Gastric Cancer Progression. Cancers 37 32349352
2019 Dipyridamole Enhances the Cytotoxicities of Trametinib against Colon Cancer Cells through Combined Targeting of HMGCS1 and MEK Pathway. Molecular cancer therapeutics 36 31554653
2021 HMGCS1 drives drug-resistance in acute myeloid leukemia through endoplasmic reticulum-UPR-mitochondria axis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 34 33601148
2024 CSN6-SPOP-HMGCS1 Axis Promotes Hepatocellular Carcinoma Progression via YAP1 Activation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 33 38308184
2023 P4HA1 activates HMGCS1 to promote nasopharyngeal carcinoma ferroptosis resistance and progression. Cellular signalling 33 36702290
2020 The mevalonate precursor enzyme HMGCS1 is a novel marker and key mediator of cancer stem cell enrichment in luminal and basal models of breast cancer. PloS one 28 32692762
2020 Umbilical cord plasma-derived exosomes from preeclamptic women induce vascular dysfunction by targeting HMGCS1 in endothelial cells. Placenta 27 33120050
2022 Ursolic acid inhibits the cholesterol biosynthesis and alleviates high fat diet-induced hypercholesterolemia via irreversible inhibition of HMGCS1 in vivo. Phytomedicine : international journal of phytotherapy and phytopharmacology 26 35671633
2017 Functional analysis of the zebrafish ortholog of HMGCS1 reveals independent functions for cholesterol and isoprenoids in craniofacial development. PloS one 23 28686747
2022 Krüppel-like Factor 13 Promotes HCC Progression by Transcriptional Regulation of HMGCS1-mediated Cholesterol Synthesis. Journal of clinical and translational hepatology 22 36381108
2022 Itraconazole Inhibits the Growth of Cutaneous Squamous Cell Carcinoma by Targeting HMGCS1/ACSL4 Axis. Frontiers in pharmacology 19 35242038
2023 VIM‑AS1 promotes proliferation and drives enzalutamide resistance in prostate cancer via IGF2BP2‑mediated HMGCS1 mRNA stabilization. International journal of oncology 16 36734275
2024 Gypenoside L inhibits hepatocellular carcinoma by targeting the SREBP2-HMGCS1 axis and enhancing immune response. Bioorganic chemistry 15 38861912
2022 MicroRNA-379-5p regulates free cholesterol accumulation and relieves diet induced-liver damage in db/db mice via STAT1/HMGCS1 axis. Molecular biomedicine 15 35945406
2022 Compartmentalized activities of HMGCS1 control cervical cancer radiosensitivity. Cellular signalling 15 36328117
2023 Gypenosides suppress hepatocellular carcinoma cells by blocking cholesterol biosynthesis through inhibition of MVA pathway enzyme HMGCS1. Chemico-biological interactions 14 37604220
2022 TET2 deficiency sensitizes tumor cells to statins by reducing HMGCS1 expression. Oncogene 12 36348011
2022 Antidiabetic drug metformin suppresses tumorigenesis through inhibition of mevalonate pathway enzyme HMGCS1. The Journal of biological chemistry 12 36356901
2019 Mutations in the zebrafish hmgcs1 gene reveal a novel function for isoprenoids during red blood cell development. Blood advances 12 30987969
2023 Ligustilide covalently binds to Cys129 of HMGCS1 to ameliorate dyslipidemia. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 11 37579692
2024 Decreased HMGCS1 inhibits proliferation and inflammatory response of keratinocytes and ameliorates imiquimod-induced psoriasis via the STAT3/IL-23 axis. International immunopharmacology 10 38608446
2023 ERRα Up-Regulates Invadopodia Formation by Targeting HMGCS1 to Promote Endometrial Cancer Invasion and Metastasis. International journal of molecular sciences 10 36835419
2024 Circular RNA HMGCS1 sponges MIR4521 to aggravate type 2 diabetes-induced vascular endothelial dysfunction. eLife 9 39235443
2025 Glutamine-driven metabolic reprogramming promotes CAR-T cell function through mTOR-SREBP2 mediated HMGCS1 upregulation in ovarian cancer. Journal of translational medicine 6 40676647
2024 circ_HMGCS1 modulates hepatocellular carcinoma chemoresistance via miR-338-5p/IL-7 pathway. Journal of cellular and molecular medicine 6 38445791
2025 Inhibition of Mettl3-mediated m6A RNA modification of HMGCS1 protects retinal ganglion cells from glutamate excitotoxicity-induced ferroptosis in a rat model of glaucoma. International journal of surgery (London, England) 5 40839015
2021 Interaction of Gal-7 with HMGCS1 In Vitro May Facilitate Cholesterol Deposition in Cultured Keratinocytes. The Journal of investigative dermatology 5 34454908
2025 HMGCS1 variants cause rigid spine syndrome amenable to mevalonic acid treatment in an animal model. Brain : a journal of neurology 4 39531736
2025 Synergistic targeting of FASN and HMGCS1 by cerulenin enhances tumor cell ferroptosis sensitivity through rewiring lipid metabolism and blocking GPX4 biosynthesis. Cancer letters 4 40848803
2025 Excess Cholesterol Biosynthesis by Up-Regulated HMGCS1 in Colorectal Cancer Cells Induced M2-Like Tumor-Associated Macrophage Polarization Via Extracellular Vesicles. Cancer research and treatment 4 41084177
2024 Targeting HMGCS1 restores chemotherapy sensitivity in acute myeloid leukemia. Blood science (Baltimore, Md.) 4 38994525
2025 RPL6 Interacts with HMGCS1 to Stabilize HIF-1α by Promoting Cholesterol Production in Hepatocellular Carcinoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 3 40650669
2025 Taurochenodeoxycholic acid suppresses the progression of glioblastoma via HMGCS1/HMGCR/GPX4 signaling pathway in vitro and in vivo. Cancer cell international 2 40264142
2024 [Inhibition of Lung Squamous Cancer Target HMGCS1 Promotes Cellular Ferroptosis]. Zhongguo fei ai za zhi = Chinese journal of lung cancer 2 38880920
2026 Mitochondrial HMGCS1 mediates cisplatin resistance in cervical cancer through regulation of mitochondrial transcription. BMC molecular and cell biology 1 41545954
2025 Genetic polymorphisms in HMGCS1 gene and its association with slaughter characteristics, meat quality, and organ coefficients in Guizhou white goats. Animal bioscience 1 39842408
2025 Melatonin enhances the function of porcine immature Sertoli cells by inhibiting the HMGCS1-estradiol pathway. Theriogenology 1 40413863
2024 Profile of key metabolites and identification of HMGCS1-DHEA pathway in porcine Sertoli cells treated by Vitamin C. The Journal of steroid biochemistry and molecular biology 1 38997072
2026 HMGCS1 as a potential mediator of resistance to EZH2 inhibition via ferroptosis mediated by PI3K/AKT/mTOR pathway in the pancreatic neuroendocrine neoplasms. Endocrine-related cancer 0 42013002
2026 Hmgcs1 regulates cholesterol synthesis and promotes nerve fiber repair after spinal cord injury. iScience 0 42111194
2026 HMGCS1 drives cholesterol-dependent membrane repair and shields tumor cells from lymphocyte attack. Nature communications 0 42248910
2025 Hypoxia-Induced Up-Regulation of ACSS2 Drives the PI3K/AKT/mTOR Pathway Through HMGCS1 to Enhance the Proliferation and Stemness of Pancreatic Cancer Cells. Discovery medicine 0 40485521
2025 Activity-based probes and chemical proteomics uncover the biological impact of targeting HMGCS1. bioRxiv : the preprint server for biology 0 40631324
2025 lncRNA EBLN3P Promotes Proliferation, Metastasis and Stemness of Gastric Cancer Cells via miR-141-3p/HMGCS1. Biochemical genetics 0 40855016

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