Details of Drug Off-Target (DOT)

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

• DOT Name: Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6)
• Synonyms: Non-specific crossreacting antigen; Normal cross-reacting antigen; CD antigen CD66c
• Gene Name: CEACAM6
• UniProt ID: CEAM6_HUMAN
• PDB ID: 4WHC; 4WTZ; 4Y8A; 4YIQ
• Pfam ID: PF13895 ; PF13927 ; PF07686
• Sequence:
  MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLPQ
  NRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTGFY
  TLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYLWWV
  NGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLYGPDVP
  TISPSKANYRPGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGSYMCQ
  AHNSATGLNRTTVTMITVSGSAPVLSAVATVGITIGVLARVALI
• Function: Cell surface glycoprotein that plays a role in cell adhesion and tumor progression. Intercellular adhesion occurs in a calcium- and fibronectin-independent manner. Mediates homophilic and heterophilic cell adhesion with other carcinoembryonic antigen-related cell adhesion molecules, such as CEACAM5 and CEACAM8. Heterophilic interaction with CEACAM8 occurs in activated neutrophils. Plays a role in neutrophil adhesion to cytokine-activated endothelial cells. Plays a role as an oncogene by promoting tumor progression; positively regulates cell migration, cell adhesion to endothelial cells and cell invasion. Also involved in the metastatic cascade process by inducing gain resistance to anoikis of pancreatic adenocarcinoma and colorectal carcinoma cells.
• Tissue Specificity: Expressed in neutrophils . Expressed in columnar epithelial and goblet cells of the colon . Expressed in numerous tumor cell lines (at protein level) .
• Reactome Pathway:
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Neutrophil degranulation (R-HSA-6798695)
  Fibronectin matrix formation (R-HSA-1566977)

Molecular Interaction Atlas (MIA) of This DOT

12 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 Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6).	[1]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6).	[7]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline decreases the expression of Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6).	[8]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6).	[9]
Coprexa	DMA0WEK	Phase 3	Coprexa decreases the expression of Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6).	[12]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6).	[11]

References

• [1] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [2] Research resource: STR DNA profile and gene expression comparisons of human BG-1 cells and a BG-1/MCF-7 clonal variant. Mol Endocrinol. 2014 Dec;28(12):2072-81.
• [3] Fetal-sex dependent genomic responses in the circulating lymphocytes of arsenic-exposed pregnant women in New Hampshire. Reprod Toxicol. 2017 Oct;73:184-195. doi: 10.1016/j.reprotox.2017.07.023. Epub 2017 Aug 6.
• [4] DNA microarray analysis of vitamin D-induced gene expression in a human colon carcinoma cell line. Physiol Genomics. 2004 Apr 13;17(2):122-9. doi: 10.1152/physiolgenomics.00002.2003.
• [5] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [6] Induction of intestinalization in human esophageal keratinocytes is a multistep process. Carcinogenesis. 2009 Jan;30(1):122-30. doi: 10.1093/carcin/bgn227. Epub 2008 Oct 8.
• [7] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [8] Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers. J Allergy Clin Immunol. 2016 Dec;138(6):1690-1700. doi: 10.1016/j.jaci.2016.02.038. Epub 2016 Apr 24.
• [9] Am80-GCSF synergizes myeloid expansion and differentiation to generate functional neutrophils that reduce neutropenia-associated infection and?mortality. EMBO Mol Med. 2016 Nov 2;8(11):1340-1359. doi: 10.15252/emmm.201606434. Print 2016 Nov.
• [10] Copper deprivation enhances the chemosensitivity of pancreatic cancer to rapamycin by mTORC1/2 inhibition. Chem Biol Interact. 2023 Sep 1;382:110546. doi: 10.1016/j.cbi.2023.110546. Epub 2023 Jun 7.
• [11] 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.
• [12] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [13] CD34+ derived macrophage and dendritic cells display differential responses to paraquat. Toxicol In Vitro. 2021 Sep;75:105198. doi: 10.1016/j.tiv.2021.105198. Epub 2021 Jun 9.