Molecule Information

General Information of the Molecule (ID: Mol04022)

• Name: Cytochrome c oxidase subunit 6B2 (COX6B2) ,Homo sapiens
• Synonyms: Cancer/testis antigen 59; Cytochrome c oxidase subunit VIb isoform 2; Cytochrome c oxidase subunit VIb, testis-specific isoform
• Molecule Type: Protein
• Gene Name: COX6B2
• Gene ID: 125965
• Location: chr19:55349306-55354719[-]
• Sequence:
  MLDVEAQEPPKGKWSTPPFDPRFPSQNQIRNCYQNFLDYHRCLKTRTRRGKSTQPCEYYF
  RVYHSLCPISWVESWNEQIKNGIFAGKI
• Function: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol- cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix. .
• Uniprot ID: CX6B2_HUMAN
• Ensembl ID: ENSG00000160471
• HGNC ID: HGNC:24380

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

Gefitinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Non-small cell lung carcinoma [ICD-11: 2C25.Y] [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Non-small cell lung carcinoma [ICD-11: 2C25.Y]
• Resistant Drug: Gefitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Nude mice , with fresh tissue from patient; Mice
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Furthermore, we revealed that targeting IGF2BP3 can markedly enhance the sensitivity of TKIs in NSCLC and this effect was strongly dependent on the coordinated induction of COX6B2, a key downstream target of IGF2BP3 in mitochondrial OXPHOS energy production. Overall, our study revealed a novel mechanism of TKI resistance involved in IGF2BP3-dependent cross-talk between epigenetic modifications and metabolic reprogramming through the IGF2BP3-COX6B2 axis in NSCLC.

Disease Class: Non-small cell lung carcinoma [ICD-11: 2C25.Y] [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Non-small cell lung carcinoma [ICD-11: 2C25.Y]
• Resistant Drug: Gefitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Nude mice , with PC-9/GR cell lines; Mice
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Furthermore, we revealed that targeting IGF2BP3 can markedly enhance the sensitivity of TKIs in NSCLC and this effect was strongly dependent on the coordinated induction of COX6B2, a key downstream target of IGF2BP3 in mitochondrial OXPHOS energy production. Overall, our study revealed a novel mechanism of TKI resistance involved in IGF2BP3-dependent cross-talk between epigenetic modifications and metabolic reprogramming through the IGF2BP3-COX6B3 axis in NSCLC.

Osimertinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Non-small cell lung carcinoma [ICD-11: 2C25.Y] [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Non-small cell lung carcinoma [ICD-11: 2C25.Y]
• Resistant Drug: Osimertinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Nude mice , with fresh tissue from patient; Mice
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Furthermore, we revealed that targeting IGF2BP3 can markedly enhance the sensitivity of TKIs in NSCLC and this effect was strongly dependent on the coordinated induction of COX6B2, a key downstream target of IGF2BP3 in mitochondrial OXPHOS energy production. Overall, our study revealed a novel mechanism of TKI resistance involved in IGF2BP3-dependent cross-talk between epigenetic modifications and metabolic reprogramming through the IGF2BP3-COX6B4 axis in NSCLC.

Disease Class: Non-small cell lung carcinoma [ICD-11: 2C25.Y] [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Non-small cell lung carcinoma [ICD-11: 2C25.Y]
• Resistant Drug: Osimertinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Nude mice , with PC-9/GR cell lines; Mice
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Furthermore, we revealed that targeting IGF2BP3 can markedly enhance the sensitivity of TKIs in NSCLC and this effect was strongly dependent on the coordinated induction of COX6B2, a key downstream target of IGF2BP3 in mitochondrial OXPHOS energy production. Overall, our study revealed a novel mechanism of TKI resistance involved in IGF2BP3-dependent cross-talk between epigenetic modifications and metabolic reprogramming through the IGF2BP3-COX6B5 axis in NSCLC.

References

• Ref 1: Metabolic Reprogramming Driven by IGF2BP3 Promotes Acquired Resistance to EGFR Inhibitors in Non-Small Cell Lung Cancer. Cancer Res. 2023 Jul 5;83(13):2187-2207.