Molecule Information

General Information of the Molecule (ID: Mol04080)

• Name: Acyl-CoA thioesterase 8 (ACOT8) ,Homo sapiens
• Synonyms: Choloyl-coenzyme A thioesterase; HIV-Nef-associated acyl-CoA thioesterase; Peroxisomal acyl-CoA thioesterase 2; Peroxisomal acyl-coenzyme A thioester hydrolase 1; Peroxisomal long-chain acyl-CoA thioesterase 1; Thioesterase II
• Molecule Type: Protein
• Gene Name: ACOT8
• Gene ID: 10005
• Location: chr20:45841721-45857405[-]
• Sequence:
  MSSPQAPEDGQGCGDRGDPPGDLRSVLVTTVLNLEPLDEDLFRGRHYWVPAKRLFGGQIV
  GQALVAAAKSVSEDVHVHSLHCYFVRAGDPKLPVLYQVERTRTGSSFSVRSVKAVQHGKP
  IFICQASFQQAQPSPMQHQFSMPTVPPPEELLDCETLIDQYLRDPNLQKRYPLALNRIAA
  QEVPIEIKPVNPSPLSQLQRMEPKQMFWVRARGYIGEGDMKMHCCVAAYISDYAFLGTAL
  LPHQWQHKVHFMVSLDHSMWFHAPFRADHWMLYECESPWAGGSRGLVHGRLWRQDGVLAV
  TCAQEGVIRVKPQVSESKL
• Function: Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels (PubMed:15194431, PubMed:9153233, PubMed:9299485). Displays no strong substrate specificity with respect to the carboxylic acid moiety of Acyl-CoAs (By similarity). Hydrolyzes medium length (C2 to C20) straight-chain, saturated and unsaturated acyl-CoAS but is inactive towards substrates with longer aliphatic chains (PubMed:9153233, PubMed:9299485). Moreover, it catalyzes the hydrolysis of CoA esters of bile acids, such as choloyl-CoA and chenodeoxycholoyl-CoA and competes with bile acid CoA:amino acid N-acyltransferase (BAAT) (By similarity). Is also able to hydrolyze CoA esters of dicarboxylic acids (By similarity). It is involved in the metabolic regulation of peroxisome proliferation (PubMed:15194431). .; (Microbial infection) May mediate Nef-induced down-regulation of CD4 cell-surface expression (PubMed:9153233). .
• Uniprot ID: ACOT8_HUMAN
• Ensembl ID: ENSG00000101473
• HGNC ID: HGNC:15919

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Orlistat

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: Orlistat
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Pancreatic cancer [ICD-11: 2C10]
• The Specified Disease: Pancreatic ductal adenocarcinoma
• The Studied Tissue: Pancreas
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.82E-14; Fold-change: 6.86E-01; Z-score: 8.55E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Nude mouse subcutaneous tumorigenic models; Mice
• Experiment for Molecule Alteration: Transcriptome sequencing and analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Mechanistically, ACOT8 regulates cellular cholesterol ester (CE) levels, decreases the levels of phosphatidylethanolamines (PEs) that bind to polyunsaturated fatty acids and promote peroxisome activation. The knockdown of ACOT8 promotes ferroptosis and increases the chemosensitivity of tumors to GEM by inducing ferroptosis-associated pathway activation in PDAC cell lines.

Disease Class: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: Orlistat
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Pancreatic cancer [ICD-11: 2C10]
• The Specified Disease: Pancreatic ductal adenocarcinoma
• The Studied Tissue: Pancreas
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.82E-14; Fold-change: 6.86E-01; Z-score: 8.55E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: AsPC1 cells; Pancreas; Homo sapiens (Human); CVCL_0152
• In Vitro Model: MiaPaCa-2 cells; Blood; Homo sapiens (Human); CVCL_0428
• In Vitro Model: Panc1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• Experiment for Molecule Alteration: Transcriptome sequencing and analysis
• Experiment for Drug Resistance: IC50 assay
• Mechanism Description: Mechanistically, ACOT8 regulates cellular cholesterol ester (CE) levels, decreases the levels of phosphatidylethanolamines (PEs) that bind to polyunsaturated fatty acids and promote peroxisome activation. The knockdown of ACOT8 promotes ferroptosis and increases the chemosensitivity of tumors to GEM by inducing ferroptosis-associated pathway activation in PDAC cell lines.

Disease Class: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: Orlistat
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Pancreatic cancer [ICD-11: 2C10]
• The Specified Disease: Pancreatic ductal adenocarcinoma
• The Studied Tissue: Pancreas
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.82E-14; Fold-change: 6.86E-01; Z-score: 8.55E+00
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: Patient-derived PDAC organoids; Homo Sapiens
• Experiment for Molecule Alteration: Transcriptome sequencing and analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Mechanistically, ACOT8 regulates cellular cholesterol ester (CE) levels, decreases the levels of phosphatidylethanolamines (PEs) that bind to polyunsaturated fatty acids and promote peroxisome activation. The knockdown of ACOT8 promotes ferroptosis and increases the chemosensitivity of tumors to GEM by inducing ferroptosis-associated pathway activation in PDAC cell lines.

Gemcitabine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: Gemcitabine
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Pancreatic cancer [ICD-11: 2C10]
• The Specified Disease: Pancreatic ductal adenocarcinoma
• The Studied Tissue: Pancreas
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.82E-14; Fold-change: 6.86E-01; Z-score: 8.55E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: ACOT8 knockdown in nude mice; ACOT8 overexpression in nude mice; Mice
• Experiment for Molecule Alteration: Transcriptome sequencing and analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Mechanistically, ACOT8 regulates cellular cholesterol ester (CE) levels, decreases the levels of phosphatidylethanolamines (PEs) that bind to polyunsaturated fatty acids and promote peroxisome activation. The knockdown of ACOT8 promotes ferroptosis and increases the chemosensitivity of tumors to GEM by inducing ferroptosis-associated pathway activation in PDAC cell lines.

Disease Class: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: Gemcitabine
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Pancreatic cancer [ICD-11: 2C10]
• The Specified Disease: Pancreatic ductal adenocarcinoma
• The Studied Tissue: Pancreas
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.82E-14; Fold-change: 6.86E-01; Z-score: 8.55E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: AsPC1 cells; Pancreas; Homo sapiens (Human); CVCL_0152
• In Vitro Model: MiaPaCa-2 cells; Blood; Homo sapiens (Human); CVCL_0428
• In Vitro Model: Panc1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• Experiment for Molecule Alteration: Transcriptome sequencing and analysis
• Experiment for Drug Resistance: IC50 assay
• Mechanism Description: Mechanistically, ACOT8 regulates cellular cholesterol ester (CE) levels, decreases the levels of phosphatidylethanolamines (PEs) that bind to polyunsaturated fatty acids and promote peroxisome activation. The knockdown of ACOT8 promotes ferroptosis and increases the chemosensitivity of tumors to GEM by inducing ferroptosis-associated pathway activation in PDAC cell lines.

Disease Class: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: Gemcitabine
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Pancreatic cancer [ICD-11: 2C10]
• The Specified Disease: Pancreatic ductal adenocarcinoma
• The Studied Tissue: Pancreas
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.82E-14; Fold-change: 6.86E-01; Z-score: 8.55E+00
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: Patient-derived PDAC organoids; Homo Sapiens
• Experiment for Molecule Alteration: Transcriptome sequencing and analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Mechanistically, ACOT8 regulates cellular cholesterol ester (CE) levels, decreases the levels of phosphatidylethanolamines (PEs) that bind to polyunsaturated fatty acids and promote peroxisome activation. The knockdown of ACOT8 promotes ferroptosis and increases the chemosensitivity of tumors to GEM by inducing ferroptosis-associated pathway activation in PDAC cell lines.

References

• Ref 1: Acyl-CoA thioesterase 8 induces gemcitabine resistance via regulation of lipid metabolism and antiferroptotic activity in pancreatic ductal adenocarcinoma. Acta Pharmacol Sin. 2025 Feb 12.