Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10459)
Regulator Name Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1)
Synonyms
3-hydroxy-3-methylglutaryl coenzyme A synthase
    Click to Show/Hide
Gene Name HMGCS1
Gene ID 3157
Regulator Type Protein coding
Uniprot ID Q01581
Sequence
MPGSLPLNAEACWPKDVGIVALEIYFPSQYVDQAELEKYDGVDAGKYTIGLGQAKMGFCT
DREDINSLCMTVVQNLMERNNLSYDCIGRLEVGTETIIDKSKSVKTNLMQLFEESGNTDI
EGIDTTNACYGGTAAVFNAVNWIESSSWDGRYALVVAGDIAVYATGNARPTGGVGAVALL
IGPNAPLIFERGLRGTHMQHAYDFYKPDMLSEYPIVDGKLSIQCYLSALDRCYSVYCKKI
HAQWQKEGNDKDFTLNDFGFMIFHSPYCKLVQKSLARMLLNDFLNDQNRDKNSIYSGLEA
FGDVKLEDTYFDRDVEKAFMKASSELFSQKTKASLLVSNQNGNMYTSSVYGSLASVLAQY
SPQQLAGKRIGVFSYGSGLAATLYSLKVTQDATPGSALDKITASLCDLKSRLDSRTGVAP
DVFAENMKLREDTHHLVNYIPQGSIDSLFEGTWYLVRVDEKHRRTYARRPTPNDDTLDEG
VGLVHSNIATEHIPSPAKKVPRLPATAAEPEAAVISNGEH

    Click to Show/Hide
Family HMG-CoA synthase family
Function
Catalyzes the condensation of acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is converted by HMG-CoA reductase (HMGCR) into mevalonate, a precursor for cholesterol synthesis.

    Click to Show/Hide
HGNC ID
HGNC:5007
KEGG ID hsa:3157
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
HMGCS1 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Browse Drug
Long-chain-fatty-acid--CoA ligase 4 (ACSL4) [Driver]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Driver
Responsed Disease Squamous cell carcinoma of skin ICD-11: 2C31
 Disease Info 
Responsed Drug Itraconazole Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model
 A-431 cells Skin squamous cell carcinoma Homo sapiens CVCL_0037
COLO 16 cells Skin squamous cell carcinoma Homo sapiens CVCL_D607
In Vivo Model
Female BALB/c nude mice (6weeks old and 18-22 g weight) were purchased from the Model Animal Research Center of Nanjing University. A431 cells (5 x 106) in cold DMEM (50 ul) were mixed with Matrigel (50 ul) and injected into mice subcutaneously. After 6 days, the tumor volume was measured and the mice were assigned to three groups. Mice were treated with either normal saline or itraconazole (40 mg/kg oral twice daily; 80 mg/kg oral twice daily).

    Click to Show/Hide
Response regulation Itraconazole inhibited the cell proliferation, induced apoptosis and blocked cell cycle of Cutaneous squamous cell carcinoma cells. And 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) and acyl-CoA synthetase long-chain family member 4 (ACSL4) were significantly upregulated in A431 cells treated with itraconazole. Itraconazole may induce ferroptosis via HMGCS1/ACSL4 axis in A431 cells.
Squamous cell carcinoma of skin [ICD-11: 2C31]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1) Protein coding
 Regulator Info 
Responsed Drug Itraconazole Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model
 A-431 cells Skin squamous cell carcinoma Homo sapiens CVCL_0037
COLO 16 cells Skin squamous cell carcinoma Homo sapiens CVCL_D607
In Vivo Model
Female BALB/c nude mice (6weeks old and 18-22 g weight) were purchased from the Model Animal Research Center of Nanjing University. A431 cells (5 x 106) in cold DMEM (50 ul) were mixed with Matrigel (50 ul) and injected into mice subcutaneously. After 6 days, the tumor volume was measured and the mice were assigned to three groups. Mice were treated with either normal saline or itraconazole (40 mg/kg oral twice daily; 80 mg/kg oral twice daily).

    Click to Show/Hide
Response regulation Itraconazole inhibited the cell proliferation, induced apoptosis and blocked cell cycle of Cutaneous squamous cell carcinoma cells. And 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) and acyl-CoA synthetase long-chain family member 4 (ACSL4) were significantly upregulated in A431 cells treated with itraconazole. Itraconazole may induce ferroptosis via HMGCS1/ACSL4 axis in A431 cells.
Itraconazole [Investigative]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Long-chain-fatty-acid--CoA ligase 4 (ACSL4) Driver
 Target Info 
Responsed Disease Squamous cell carcinoma of skin ICD-11: 2C31
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model
 A-431 cells Skin squamous cell carcinoma Homo sapiens CVCL_0037
COLO 16 cells Skin squamous cell carcinoma Homo sapiens CVCL_D607
In Vivo Model
Female BALB/c nude mice (6weeks old and 18-22 g weight) were purchased from the Model Animal Research Center of Nanjing University. A431 cells (5 x 106) in cold DMEM (50 ul) were mixed with Matrigel (50 ul) and injected into mice subcutaneously. After 6 days, the tumor volume was measured and the mice were assigned to three groups. Mice were treated with either normal saline or itraconazole (40 mg/kg oral twice daily; 80 mg/kg oral twice daily).

    Click to Show/Hide
Response regulation Itraconazole inhibited the cell proliferation, induced apoptosis and blocked cell cycle of Cutaneous squamous cell carcinoma cells. And 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) and acyl-CoA synthetase long-chain family member 4 (ACSL4) were significantly upregulated in A431 cells treated with itraconazole. Itraconazole may induce ferroptosis via HMGCS1/ACSL4 axis in A431 cells.
References
Ref 1 Itraconazole Inhibits the Growth of Cutaneous Squamous Cell Carcinoma by Targeting HMGCS1/ACSL4 Axis. Front Pharmacol. 2022 Feb 15;13:828983. doi: 10.3389/fphar.2022.828983. eCollection 2022.