Molecule Information

General Information of the Molecule (ID: Mol04107)

• Name: Family with sequence similarity 83 member B (FAM83B) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: FAM83B
• Gene ID: 222584
• Location: chr6:54846771-54945099[+]
• Sequence:
  METSSMLSSLNDECKSDNYIEPHYKEWYRVAIDILIEHGLEAYQEFLVQERVSDFLAEEE
  INYILKNVQKVAQSTAHGTDDSCDDTLSSGTYWPVESDVEAPNLDLGWPYVMPGLLGGTH
  IDLLFHPPRAHLLTIKETIRKMIKEARKVIALVMDIFTDVDIFKEIVEASTRGVSVYILL
  DESNFNHFLNMTEKQGCSVQRLRNIRVRTVKGQDYLSKTGAKFHGKMEQKFLLVDCQKVM
  YGSYSYMWSFEKAHLSMVQIITGQLVESFDEEFRTLYARSCVPSSFAQEESARVKHGKAL
  WENGTYQHSVSSLASVSSQRNLFGRQDKIHKLDSSYFKNRGIYTLNEHDKYNIRSHGYKP
  HFVPNFNGPNAIRQFQPNQINENWKRHSYAGEQPETVPYLLLNRALNRTNNPPGNWKKPS
  DSLSVASSSREGYVSHHNTPAQSFANRLAQRKTTNLADRNSNVRRSFNGTDNHIRFLQQR
  MPTLEHTTKSFLRNWRIESYLNDHSEATPDSNGSALGDRFEGYDNPENLKANALYTHSRL
  RSSLVFKPTLPEQKEVNSCTTGSSNSTIIGSQGSETPKEVPDTPTNVQHLTDKPLPESIP
  KLPLQSEAPKMHTLQVPENHSVALNQTTNGHTESNNYIYKTLGVNKQTENLKNQQTENLL
  KRRSFPLFDNSKANLDPGNSKHYVYSTLTRNRVRQPEKPKEDLLKSSKSMHNVTHNLEED
  EEEVTKRNSPSGTTTKSVSIAALLDVNKEESNKELASKKEVKGSPSFLKKGSQKLRSLLS
  LTPDKKENLSKNKAPAFYRLCSSSDTLVSEGEENQKPKKSDTKVDSSPRRKHSSSSNSQG
  SIHKSKEDVTVSPSQEINAPPDENKRTPSPGPVESKFLERAGDASAPRFNTEQIQYRDSR
  EINAVVTPERRPTSSPRPTSSELLRSHSTDRRVYSRFEPFCKIESSIQPTSNMPNTSINR
  PEIKSATMGNSYGRSSPLLNYNTGVYRSYQPNENKFRGFMQKFGNFIHKNK
• 3D-structure: PDB ID: 5LZK; Classification: Structural genomics; Method: X-ray diffraction; Resolution: 1.57 Å
• Function: Probable proto-oncogene that functions in the epidermal growth factor receptor/EGFR signaling pathway. Activates both the EGFR itself and downstream RAS/MAPK and PI3K/AKT/TOR signaling cascades. .
• Uniprot ID: FA83B_HUMAN
• Ensembl ID: ENSG00000168143
• HGNC ID: HGNC:21357

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

Pemetrexed

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Lung adenocarcinoma [ICD-11: 2C25.0] [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Resistant Drug: Pemetrexed
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung adenocarcinoma
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.89E-39; Fold-change: 1.68E+00; Z-score: 1.75E+01
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: PC-9 cells; Lung; Homo sapiens (Human); CVCL_B260
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: The mechanistic analysis demonstrated that FAM83B impedes the translocation of calbindin 2 (CALB2) from the cytoplasm to the mitochondria, resulting in the inhibition of apoptosis and the promotion of mitochondrial activity. Consequently, this ultimately confers resistance to chemotherapy in LUAD. Furthermore, the administration of metformin, which blocks mitochondrial oxidative phosphorylation (OXPHOS), can restore sensitivity to drug resistance in LUAD. Taken together, these findings provide substantial evidence supporting the notion that FAM83B enhances chemotherapy resistance in LUAD through the upregulation of mitochondrial metabolism and the inhibition of apoptosis.

Osimertinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Lung adenocarcinoma [ICD-11: 2C25.0] [2]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Resistant Drug: Osimertinib
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung adenocarcinoma
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.89E-39; Fold-change: 1.68E+00; Z-score: 1.75E+01
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A431 cells; Skin; Homo sapiens (Human); CVCL_0037
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: PI/Annexin V apoptosis assay
• Mechanism Description: Mechanically, Osi treatment induces an elevation of NCOA4, a key protein of ferritinophagy, which maintains the synthesis of iron-sulfur cluster (ISC) proteins of electron transport chain and OXPHOS. Additionally, active ISC protein synthesis in adaptive-resistant cells significantly increases the sensitivity to copper ions. Combining Osi with elesclomol, a copper ion ionophore, significantly increases the efficacy of Osi, with no additional toxicity. Altogether, this study reveals the mechanisms of NCOA9-mediated ferritinophagy in Osi adaptive resistance and introduces a promising new therapy of combining copper ionophores to improve its initial efficacy.

Disease Class: Lung adenocarcinoma [ICD-11: 2C25.0] [2]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Resistant Drug: Osimertinib
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung adenocarcinoma
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.89E-39; Fold-change: 1.68E+00; Z-score: 1.75E+01
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: H1650 cells; Pleural effusion; Homo sapiens (Human); CVCL_4V01
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: PI/Annexin V apoptosis assay
• Mechanism Description: Mechanically, Osi treatment induces an elevation of NCOA4, a key protein of ferritinophagy, which maintains the synthesis of iron-sulfur cluster (ISC) proteins of electron transport chain and OXPHOS. Additionally, active ISC protein synthesis in adaptive-resistant cells significantly increases the sensitivity to copper ions. Combining Osi with elesclomol, a copper ion ionophore, significantly increases the efficacy of Osi, with no additional toxicity. Altogether, this study reveals the mechanisms of NCOA8-mediated ferritinophagy in Osi adaptive resistance and introduces a promising new therapy of combining copper ionophores to improve its initial efficacy.

Disease Class: Lung adenocarcinoma [ICD-11: 2C25.0] [2]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Resistant Drug: Osimertinib
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung adenocarcinoma
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.89E-39; Fold-change: 1.68E+00; Z-score: 1.75E+01
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCC4006 cells; Lung; Homo sapiens (Human); CVCL_1269
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: PI/Annexin V apoptosis assay
• Mechanism Description: Mechanically, Osi treatment induces an elevation of NCOA4, a key protein of ferritinophagy, which maintains the synthesis of iron-sulfur cluster (ISC) proteins of electron transport chain and OXPHOS. Additionally, active ISC protein synthesis in adaptive-resistant cells significantly increases the sensitivity to copper ions. Combining Osi with elesclomol, a copper ion ionophore, significantly increases the efficacy of Osi, with no additional toxicity. Altogether, this study reveals the mechanisms of NCOA7-mediated ferritinophagy in Osi adaptive resistance and introduces a promising new therapy of combining copper ionophores to improve its initial efficacy.

Disease Class: Lung adenocarcinoma [ICD-11: 2C25.0] [2]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Resistant Drug: Osimertinib
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung adenocarcinoma
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.89E-39; Fold-change: 1.68E+00; Z-score: 1.75E+01
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: PC-9 cells; Lung; Homo sapiens (Human); CVCL_B260
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: PI/Annexin V apoptosis assay
• Mechanism Description: Mechanically, Osi treatment induces an elevation of NCOA4, a key protein of ferritinophagy, which maintains the synthesis of iron-sulfur cluster (ISC) proteins of electron transport chain and OXPHOS. Additionally, active ISC protein synthesis in adaptive-resistant cells significantly increases the sensitivity to copper ions. Combining Osi with elesclomol, a copper ion ionophore, significantly increases the efficacy of Osi, with no additional toxicity. Altogether, this study reveals the mechanisms of NCOA6-mediated ferritinophagy in Osi adaptive resistance and introduces a promising new therapy of combining copper ionophores to improve its initial efficacy.

Disease Class: Lung adenocarcinoma [ICD-11: 2C25.0] [2]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Resistant Drug: Osimertinib
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung adenocarcinoma
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.89E-39; Fold-change: 1.68E+00; Z-score: 1.75E+01
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: PI/Annexin V apoptosis assay
• Mechanism Description: Mechanically, Osi treatment induces an elevation of NCOA4, a key protein of ferritinophagy, which maintains the synthesis of iron-sulfur cluster (ISC) proteins of electron transport chain and OXPHOS. Additionally, active ISC protein synthesis in adaptive-resistant cells significantly increases the sensitivity to copper ions. Combining Osi with elesclomol, a copper ion ionophore, significantly increases the efficacy of Osi, with no additional toxicity. Altogether, this study reveals the mechanisms of NCOA5-mediated ferritinophagy in Osi adaptive resistance and introduces a promising new therapy of combining copper ionophores to improve its initial efficacy.

References

• Ref 1: FAM83B regulates mitochondrial metabolism and anti-apoptotic activity in pulmonary adenocarcinoma. Apoptosis. 2024 Jun;29(5-6):743-756.
• Ref 2: Ferritinophagy mediates adaptive resistance to EGFR tyrosine kinase inhibitors in non-small cell lung cancer. Nat Commun. 2024 May 17;15(1):4195.