Molecule Information

General Information of the Molecule (ID: Mol04081)

• Name: Acylphosphatase 1 (ACYP1) ,Homo sapiens
• Synonyms: Acylphosphatase, erythrocyte isozyme; Acylphosphatase, organ-common type isozyme; Acylphosphate phosphohydrolase 1
• Molecule Type: Protein
• Gene Name: ACYP1
• Gene ID: 97
• Location: chr14:75053237-75069483[-]
• Sequence:
  MAEGNTLISVDYEIFGKVQGVFFRKHTQAEGKKLGLVGWVQNTDRGTVQGQLQGPISKVR
  HMQEWLETRGSPKSHIDKANFNNEKVILKLDYSDFQIVK
• 3D-structure: PDB ID: 2VH7; Classification: Hydrolase; Method: X-ray diffraction; Resolution: 1.45 Å
• Uniprot ID: ACYP1_HUMAN
• Ensembl ID: ENSG00000119640
• HGNC ID: HGNC:179

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) 1 drug(s) in total

Lenvatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Resistant Drug: Lenvatinib
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Liver cancer [ICD-11: 2C12]
• The Specified Disease: Hepatocellular carcinoma
• The Studied Tissue: Liver tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.80E-05; Fold-change: 2.38E-01; Z-score: 4.38E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: LvACYP1 Hep3B cells lung metastasis model; LvACYP1 Hep3B cells xenograft model; LvCON Hep3B cells lung metastasis model; LvCON Hep3B cells xenograft model; Mice
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Mechanistically, ACYP1 enhanced glycolysis by upregulating the expression of LDHA, and the upregulation of LDHA is MYC-dependent. Additionally, the stability of c-Myc can be attributed to the interaction of ACYP1 and HSP90. More importantly, the ACYP1/HSP90/MYC/LDHA axis is associated with lenvatinib resistance in HCC cells.

Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Resistant Drug: Lenvatinib
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Liver cancer [ICD-11: 2C12]
• The Specified Disease: Hepatocellular carcinoma
• The Studied Tissue: Liver tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.80E-05; Fold-change: 2.38E-01; Z-score: 4.38E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: Huh7 cells; Kidney; Homo sapiens (Human); CVCL_U442
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTS assay; Cell colony formation assay
• Mechanism Description: Mechanistically, ACYP1 enhanced glycolysis by upregulating the expression of LDHA, and the upregulation of LDHA is MYC-dependent. Additionally, the stability of c-Myc can be attributed to the interaction of ACYP1 and HSP90. More importantly, the ACYP1/HSP90/MYC/LDHA axis is associated with lenvatinib resistance in HCC cells.

Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Resistant Drug: Lenvatinib
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Liver cancer [ICD-11: 2C12]
• The Specified Disease: Hepatocellular carcinoma
• The Studied Tissue: Liver tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.80E-05; Fold-change: 2.38E-01; Z-score: 4.38E+00
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: HCC patients; Homo Sapiens
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: Overall survival assay (OS)
• Mechanism Description: Mechanistically, ACYP1 enhanced glycolysis by upregulating the expression of LDHA, and the upregulation of LDHA is MYC-dependent. Additionally, the stability of c-Myc can be attributed to the interaction of ACYP1 and HSP90. More importantly, the ACYP1/HSP90/MYC/LDHA axis is associated with lenvatinib resistance in HCC cells.

Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Resistant Drug: Lenvatinib
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Liver cancer [ICD-11: 2C12]
• The Specified Disease: Hepatocellular carcinoma
• The Studied Tissue: Liver tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.80E-05; Fold-change: 2.38E-01; Z-score: 4.38E+00
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: HCC patients; Homo Sapiens
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Mechanistically, ACYP1 enhanced glycolysis by upregulating the expression of LDHA, and the upregulation of LDHA is MYC-dependent. Additionally, the stability of c-Myc can be attributed to the interaction of ACYP1 and HSP90. More importantly, the ACYP1/HSP90/MYC/LDHA axis is associated with lenvatinib resistance in HCC cells.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [1]

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Sensitive Drug: Lenvatinib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: ACYP1 overexpression cells; Liver; Homo sapiens (Human); N.A.
• In Vitro Model: SK-Hep1 cells; Ascites; Homo sapiens (Human); CVCL_0525
• In Vivo Model: ACYP1 knockdown nude mice; Mice
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Mechanistically, ACYP1 enhanced glycolysis by upregulating the expression of LDHA, and the upregulation of LDHA is MYC-dependent. Additionally, the stability of c-Myc can be attributed to the interaction of ACYP1 and HSP90. More importantly, the ACYP1/HSP90/MYC/LDHA axis is associated with lenvatinib resistance in HCC cells.

References

• Ref 1: Targeting ACYP1-mediated glycolysis reverses lenvatinib resistance and restricts hepatocellular carcinoma progression. Drug Resist Updat. 2023 Jul;69:100976.