Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBI16V7)

• DOT Name: Protein FAM83A (FAM83A)
• Synonyms: Tumor antigen BJ-TSA-9; Tumor-specific gene expressed in prostate protein
• Gene Name: FAM83A
• Related Disease:
  Hepatocellular carcinoma
  Adenocarcinoma
  Advanced cancer
  Lung neoplasm
  Non-alcoholic fatty liver disease
  Breast cancer
  Breast carcinoma
  Pancreatic cancer
  Lung adenocarcinoma
  Metastatic malignant neoplasm
  Neoplasm
  Non-small-cell lung cancer
• UniProt ID: FA83A_HUMAN
• PDB ID: 4URJ
• Pfam ID: PF07894
• Sequence:
  MSRSRHLGKIRKRLEDVKSQWVRPARADFSDNESARLATDALLDGGSEAYWRVLSQEGEV
  DFLSSVEAQYIQAQAREPPCPPDTLGGAEAGPKGLDSSSLQSGTYFPVASEGSEPALLHS
  WASAEKPYLKEKSSATVYFQTVKHNNIRDLVRRCITRTSQVLVILMDVFTDVEIFCDILE
  AANKRGVFVCVLLDQGGVKLFQEMCDKVQISDSHLKNISIRSVEGEIYCAKSGRKFAGQI
  REKFIISDWRFVLSGSYSFTWLCGHVHRNILSKFTGQAVELFDEEFRHLYASSKPVMGLK
  SPRLVAPVPPGAAPANGRLSSSSGSASDRTSSNPFSGRSAGSHPGTRSVSASSGPCSPAA
  PHPPPPPRFQPHQGPWGAPSPQAHLSPRPHDGPPAAVYSNLGAYRPTRLQLEQLGLVPRL
  TPTWRPFLQASPHF
• Function: Probable proto-oncogene that functions in the epidermal growth factor receptor/EGFR signaling pathway. Activates both RAS/MAPK and PI3K/AKT/TOR signaling cascades downstream of EGFR. Required for the RAS/MAPK signaling cascade activation upon EGFR stimulation, it also activates both signaling cascades independently of EGFR activation.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Lung neoplasm	DISVARNB	Strong	Biomarker	[4]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[6]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[6]
Pancreatic cancer	DISJC981	moderate	Biomarker	[7]
Lung adenocarcinoma	DISD51WR	Limited	Altered Expression	[8]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[3]
Neoplasm	DISZKGEW	Limited	Altered Expression	[8]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[9]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Protein FAM83A (FAM83A).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein FAM83A (FAM83A).	[14]

5 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein FAM83A (FAM83A).	[11]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein FAM83A (FAM83A).	[12]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Protein FAM83A (FAM83A).	[13]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Protein FAM83A (FAM83A).	[15]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Protein FAM83A (FAM83A).	[16]

References

• [1] Long noncoding RNA FAM83A-AS1 facilitates hepatocellular carcinoma progression by binding with NOP58 to enhance the mRNA stability of FAM83A.Biosci Rep. 2019 Nov 29;39(11):BSR20192550. doi: 10.1042/BSR20192550.
• [2] A FAM83A Positive Feed-back Loop Drives Survival and Tumorigenicity of Pancreatic Ductal Adenocarcinomas.Sci Rep. 2019 Sep 16;9(1):13396. doi: 10.1038/s41598-019-49475-5.
• [3] FAM83A signaling induces epithelial-mesenchymal transition by the PI3K/AKT/Snail pathway in NSCLC.Aging (Albany NY). 2019 Aug 24;11(16):6069-6088. doi: 10.18632/aging.102163. Epub 2019 Aug 24.
• [4] Detection of circulating cancer cells in lung cancer patients with a panel of marker genes.Biochem Biophys Res Commun. 2008 Aug 8;372(4):756-60. doi: 10.1016/j.bbrc.2008.05.101. Epub 2008 Jun 2.
• [5] Effect of a stilbene glycoside-rich extract from Polygoni Multiflori Radix on experimental non-alcoholic fatty liver disease based on principal component and orthogonal partial least squares discriminant analysis.Exp Ther Med. 2017 Nov;14(5):4958-4966. doi: 10.3892/etm.2017.5197. Epub 2017 Sep 22.
• [6] FAM83A confers EGFR-TKI resistance in breast cancer cells and in mice.J Clin Invest. 2012 Sep;122(9):3211-20. doi: 10.1172/JCI60498. Epub 2012 Aug 13.
• [7] FAM83A is amplified and promotes cancer stem cell-like traits and chemoresistance in pancreatic cancer.Oncogenesis. 2017 Mar 13;6(3):e300. doi: 10.1038/oncsis.2017.3.
• [8] Elevated FAM83A expression predicts poorer clincal outcome in lung adenocarcinoma.Cancer Biomark. 2019;26(3):367-373. doi: 10.3233/CBM-190520.
• [9] Long noncoding antisense RNA FAM83A-AS1 promotes lung cancer cell progression by increasing FAM83A.J Cell Biochem. 2019 Jun;120(6):10505-10512. doi: 10.1002/jcb.28336. Epub 2019 Jan 18.
• [10] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [11] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [12] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [13] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [14] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [15] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [16] Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.