Molecule Information

General Information of the Molecule (ID: Mol04125)

• Name: Mal, T-cell differentiation protein 2 (MAL2) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: MAL2
• Gene ID: 114569
• Location: chr8:119165034-119245673[+]
• Sequence:
  MSAGGASVPPPPNPAVSFPPPRVTLPAGPDILRTYSGAFVCLEILFGGLVWILVASSNVP
  LPLLQGWVMFVSVTAFFFSLLFLGMFLSGMVAQIDANWNFLDFAYHFTVFVFYFGAFLLE
  AAATSLHDLHCNTTITGQPLLSDNQYNINVAASIFAFMTTACYGCSLGLALRRWRP
• Function: Member of the machinery of polarized transport. Required for the indirect transcytotic route at the step of the egress of the transcytosing cargo from perinuclear endosomes in order for it to travel to the apical surface via a raft-dependent pathway. .
• Uniprot ID: MAL2_HUMAN
• Ensembl ID: ENSG00000147676
• HGNC ID: HGNC:13634

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

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: EGFR tyrosine kinase inhibitor resistance; Activation; hsa01521
• Cell Pathway Regulation: Alcoholic liver disease; Activation; hsa04936
• In Vitro Model: HuCCT1 cells; Bile duct; Homo sapiens (Human); CVCL_0324
• In Vitro Model: RBE cells; Liver; Homo sapiens (Human); CVCL_4896
• Experiment for Molecule Alteration: ScRNA-seq
• Experiment for Drug Resistance: CCK8 assay; Edu test assay
• Mechanism Description: Our research unequivocally underscores the critical role of MAL2 as an oncogenic promoter in ICC. Upon exposure to EGF, MAL2 exhibits its ability to retain EGFR on the cell surface, thwarting the endocytosis process. This action consecutively triggers the PI3K/AKT/SREBP-1 signaling cascade, inciting an increase in lipid deposition within ICC cells.

Disease Class: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: EGFR tyrosine kinase inhibitor resistance; Activation; hsa01521
• Cell Pathway Regulation: Alcoholic liver disease; Activation; hsa04936
• In Vitro Model: HUCCT1 transfected with sh-MAL2; Liver; Homo sapiens (Human); CVCL_0324
• In Vitro Model: HUCCT1 transfected with sh-NC; Liver; Homo sapiens (Human); CVCL_0324
• In Vitro Model: RBE cells transfected with sh-MAL2; Liver; Homo sapiens (Human); CVCL_4896
• In Vitro Model: RBE cells transfected with sh-NC; Liver; Homo sapiens (Human); CVCL_4896
• Experiment for Molecule Alteration: ScRNA-seq
• Experiment for Drug Resistance: IC50 assay
• Mechanism Description: Our research unequivocally underscores the critical role of MAL2 as an oncogenic promoter in ICC. Upon exposure to EGF, MAL2 exhibits its ability to retain EGFR on the cell surface, thwarting the endocytosis process. This action consecutively triggers the PI3K/AKT/SREBP-1 signaling cascade, inciting an increase in lipid deposition within ICC cells.

Disease Class: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: EGFR tyrosine kinase inhibitor resistance; Activation; hsa01521
• Cell Pathway Regulation: Alcoholic liver disease; Activation; hsa04936
• In Vivo Model: 6-week-old BALB/c nude mice; 6-week-old BALB/c nude mice which were subcutaneously administered 1????106 transfected HUCCT1 cells ; liver orthotopic-implantation models, 3????106 HUCCT1 cells were injected into the liver; Mice
• Experiment for Molecule Alteration: ScRNA-seq
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Our research unequivocally underscores the critical role of MAL2 as an oncogenic promoter in ICC. Upon exposure to EGF, MAL2 exhibits its ability to retain EGFR on the cell surface, thwarting the endocytosis process. This action consecutively triggers the PI3K/AKT/SREBP-1 signaling cascade, inciting an increase in lipid deposition within ICC cells.

References

• Ref 1: MAL2 reprograms lipid metabolism in intrahepatic cholangiocarcinoma via EGFR/SREBP-1 pathway based on single-cell RNA sequencing. Cell Death Dis. 2024 Jun 12;15(6):411.