Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD7RRWK)

• DOT Name: CUB domain-containing protein 1 (CDCP1)
• Synonyms: Membrane glycoprotein gp140; Subtractive immunization M plus HEp3-associated 135 kDa protein; SIMA135; Transmembrane and associated with src kinases; CD antigen CD318
• Gene Name: CDCP1
• Related Disease:
  Arthritis
  Autoimmune disease
  Blast phase chronic myelogenous leukemia, BCR-ABL1 positive
  Breast neoplasm
  Carcinoma of esophagus
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Drug dependence
  Epithelial ovarian cancer
  Esophageal cancer
  Esophageal squamous cell carcinoma
  HER2/NEU overexpressing breast cancer
  Hyperlipidemia
  Kidney cancer
  Lung adenocarcinoma
  Lung carcinoma
  Lung neoplasm
  Melanoma
  Metastatic malignant neoplasm
  Multiple sclerosis
  Myocardial infarction
  Myopathy
  Neoplasm
  Neoplasm of esophagus
  Nervous system inflammation
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Pulmonary fibrosis
  Renal carcinoma
  Rheumatoid arthritis
  Substance abuse
  Substance dependence
  Carcinoma
  Lung cancer
  Triple negative breast cancer
  Adenocarcinoma
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Pancreatic cancer
  Renal cell carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: CDCP1_HUMAN
• Sequence:
  MAGLNCGVSIALLGVLLLGAARLPRGAEAFEIALPRESNITVLIKLGTPTLLAKPCYIVI
  SKRHITMLSIKSGERIVFTFSCQSPENHFVIEIQKNIDCMSGPCPFGEVQLQPSTSLLPT
  LNRTFIWDVKAHKSIGLELQFSIPRLRQIGPGESCPDGVTHSISGRIDATVVRIGTFCSN
  GTVSRIKMQEGVKMALHLPWFHPRNVSGFSIANRSSIKRLCIIESVFEGEGSATLMSANY
  PEGFPEDELMTWQFVVPAHLRASVSFLNFNLSNCERKEERVEYYIPGSTTNPEVFKLEDK
  QPGNMAGNFNLSLQGCDQDAQSPGILRLQFQVLVQHPQNESNKIYVVDLSNERAMSLTIE
  PRPVKQSRKFVPGCFVCLESRTCSSNLTLTSGSKHKISFLCDDLTRLWMNVEKTISCTDH
  RYCQRKSYSLQVPSDILHLPVELHDFSWKLLVPKDRLSLVLVPAQKLQQHTHEKPCNTSF
  SYLVASAIPSQDLYFGSFCPGGSIKQIQVKQNISVTLRTFAPSFQQEASRQGLTVSFIPY
  FKEEGVFTVTPDTKSKVYLRTPNWDRGLPSLTSVSWNISVPRDQVACLTFFKERSGVVCQ
  TGRAFMIIQEQRTRAEEIFSLDEDVLPKPSFHHHSFWVNISNCSPTSGKQLDLLFSVTLT
  PRTVDLTVILIAAVGGGVLLLSALGLIICCVKKKKKKTNKGPAVGIYNDNINTEMPRQPK
  KFQKGRKDNDSHVYAVIEDTMVYGHLLQDSSGSFLQPEVDTYRPFQGTMGVCPPSPPTIC
  SRAPTAKLATEEPPPRSPPESESEPYTFSHPNNGDVSSKDTDIPLLNTQEPMEPAE
• Function: May be involved in cell adhesion and cell matrix association. May play a role in the regulation of anchorage versus migration or proliferation versus differentiation via its phosphorylation. May be a novel marker for leukemia diagnosis and for immature hematopoietic stem cell subsets. Belongs to the tetraspanin web involved in tumor progression and metastasis.
• Tissue Specificity: Highly expressed in mitotic cells with low expression during interphase. Detected at highest levels in skeletal muscle and colon with lower levels in kidney, small intestine, placenta and lung. Up-regulated in a number of human tumor cell lines, as well as in colorectal cancer, breast carcinoma and lung cancer. Also expressed in cells with phenotypes reminiscent of mesenchymal stem cells and neural stem cells.

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arthritis	DIST1YEL	Strong	Biomarker	[1]
Autoimmune disease	DISORMTM	Strong	Biomarker	[1]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Strong	Altered Expression	[2]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[3]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[4]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[5]
Colon cancer	DISVC52G	Strong	Altered Expression	[6]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Drug dependence	DIS9IXRC	Strong	Biomarker	[8]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[9]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[4]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[4]
HER2/NEU overexpressing breast cancer	DISYKID5	Strong	Biomarker	[3]
Hyperlipidemia	DIS61J3S	Strong	Biomarker	[10]
Kidney cancer	DISBIPKM	Strong	Biomarker	[11]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[12]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[13]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[14]
Melanoma	DIS1RRCY	Strong	Biomarker	[15]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[12]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[16]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[10]
Myopathy	DISOWG27	Strong	Genetic Variation	[17]
Neoplasm	DISZKGEW	Strong	Biomarker	[18]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[4]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[16]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[9]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[9]
Prostate cancer	DISF190Y	Strong	Biomarker	[18]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[18]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[19]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[20]
Renal carcinoma	DISER9XT	Strong	Biomarker	[11]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[1]
Substance abuse	DIS327VW	Strong	Biomarker	[8]
Substance dependence	DISDRAAR	Strong	Biomarker	[8]
Carcinoma	DISH9F1N	moderate	Biomarker	[21]
Lung cancer	DISCM4YA	moderate	Genetic Variation	[13]
Triple negative breast cancer	DISAMG6N	moderate	Altered Expression	[22]
Adenocarcinoma	DIS3IHTY	Disputed	Altered Expression	[23]
Bladder cancer	DISUHNM0	Limited	Biomarker	[24]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[22]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[22]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[25]
Renal cell carcinoma	DISQZ2X8	Limited	Altered Expression	[11]
Urinary bladder cancer	DISDV4T7	Limited	Biomarker	[24]
Urinary bladder neoplasm	DIS7HACE	Limited	Biomarker	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of CUB domain-containing protein 1 (CDCP1).	[26]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of CUB domain-containing protein 1 (CDCP1).	[27]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of CUB domain-containing protein 1 (CDCP1).	[28]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CUB domain-containing protein 1 (CDCP1).	[29]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of CUB domain-containing protein 1 (CDCP1).	[30]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of CUB domain-containing protein 1 (CDCP1).	[31]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of CUB domain-containing protein 1 (CDCP1).	[32]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of CUB domain-containing protein 1 (CDCP1).	[33]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of CUB domain-containing protein 1 (CDCP1).	[34]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of CUB domain-containing protein 1 (CDCP1).	[35]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of CUB domain-containing protein 1 (CDCP1).	[36]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of CUB domain-containing protein 1 (CDCP1).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of CUB domain-containing protein 1 (CDCP1).	[38]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of CUB domain-containing protein 1 (CDCP1).	[39]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of CUB domain-containing protein 1 (CDCP1).	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of CUB domain-containing protein 1 (CDCP1).	[40]

References

• [1] CD318 is a ligand for CD6.Proc Natl Acad Sci U S A. 2017 Aug 15;114(33):E6912-E6921. doi: 10.1073/pnas.1704008114. Epub 2017 Jul 31.
• [2] CDCP1 identifies a broad spectrum of normal and malignant stem/progenitor cell subsets of hematopoietic and nonhematopoietic origin.Stem Cells. 2004;22(3):334-43. doi: 10.1634/stemcells.22-3-334.
• [3] Interaction of CDCP1 with HER2 enhances HER2-driven tumorigenesis and promotes trastuzumab resistance in breast cancer.Cell Rep. 2015 Apr 28;11(4):564-76. doi: 10.1016/j.celrep.2015.03.044. Epub 2015 Apr 16.
• [4] Loss of CDCP1 expression promotes invasiveness and poor prognosis in esophageal squamous cell carcinoma.Ann Surg Oncol. 2014 Dec;21 Suppl 4:S640-7. doi: 10.1245/s10434-014-3740-4. Epub 2014 May 22.
• [5] Identification of CDCP1 as a hypoxia-inducible factor 2 (HIF-2) target gene that is associated with survival in clear cell renal cell carcinoma patients.Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3483-8. doi: 10.1073/pnas.1222435110. Epub 2013 Feb 1.
• [6] CUB domain containing protein 1 (CDCP1) modulates adhesion and motility in colon cancer cells.BMC Cancer. 2014 Oct 9;14:754. doi: 10.1186/1471-2407-14-754.
• [7] CDCP1 enhances Wnt signaling in colorectal cancer promoting nuclear localization of -catenin and E-cadherin.Oncogene. 2020 Jan;39(1):219-233. doi: 10.1038/s41388-019-0983-3. Epub 2019 Aug 30.
• [8] Genome wide association for addiction: replicated results and comparisons of two analytic approaches.PLoS One. 2010 Jan 21;5(1):e8832. doi: 10.1371/journal.pone.0008832.
• [9] MicroRNA-654-5p suppresses ovarian cancer development impacting on MYC, WNT and AKT pathways.Oncogene. 2019 Aug;38(32):6035-6050. doi: 10.1038/s41388-019-0860-0. Epub 2019 Jul 5.
• [10] Genetic copy number variants in myocardial infarction patients with hyperlipidemia.BMC Genomics. 2011 Nov 30;12 Suppl 3(Suppl 3):S23. doi: 10.1186/1471-2164-12-S3-S23. Epub 2011 Nov 30.
• [11] VHL loss in renal cell carcinoma leads to up-regulation of CUB domain-containing protein 1 to stimulate PKC{delta}-driven migration.Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):1931-6. doi: 10.1073/pnas.1011777108. Epub 2011 Jan 13.
• [12] Homophilic complex formation of CDCP1 via the extracellular CUB2 domain facilitates SFK activation and promotes cancer cell migration.Oncol Rep. 2019 Oct;42(4):1507-1516. doi: 10.3892/or.2019.7271. Epub 2019 Aug 8.
• [13] Common Co-activation of AXL and CDCP1 in EGFR-mutation-positive Non-smallcell Lung Cancer Associated With Poor Prognosis.EBioMedicine. 2018 Mar;29:112-127. doi: 10.1016/j.ebiom.2018.02.001. Epub 2018 Feb 5.
• [14] ADAM9 enhances CDCP1 protein expression by suppressing miR-218 for lung tumor metastasis.Sci Rep. 2015 Nov 10;5:16426. doi: 10.1038/srep16426.
• [15] CUB-domain-containing protein 1 (CDCP1) activates Src to promote melanoma metastasis.Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1379-84. doi: 10.1073/pnas.1017228108. Epub 2011 Jan 10.
• [16] Clinical and experimental evidence for targeting CD6 in immune-based disorders.Autoimmun Rev. 2018 May;17(5):493-503. doi: 10.1016/j.autrev.2017.12.004. Epub 2018 Mar 9.
• [17] Genomewide Association Study of Statin-Induced Myopathy in Patients Recruited Using the UK Clinical Practice Research Datalink.Clin Pharmacol Ther. 2019 Dec;106(6):1353-1361. doi: 10.1002/cpt.1557. Epub 2019 Jul 31.
• [18] Regulation of inside-out 1-integrin activation by CDCP1.Oncogene. 2018 May;37(21):2817-2836. doi: 10.1038/s41388-018-0142-2. Epub 2018 Mar 7.
• [19] Targeting CUB domain-containing protein 1 with a monoclonal antibody inhibits metastasis in a prostate cancer model.Cancer Res. 2008 May 15;68(10):3759-66. doi: 10.1158/0008-5472.CAN-07-1657.
• [20] Cub domain-containing protein 1 negatively regulates TGF- signaling and myofibroblast differentiation.Am J Physiol Lung Cell Mol Physiol. 2018 May 1;314(5):L695-L707. doi: 10.1152/ajplung.00205.2017. Epub 2018 Jan 4.
• [21] CDCP1 cleavage is necessary for homodimerization-induced migration of triple-negative breast cancer.Oncogene. 2016 Sep 8;35(36):4762-72. doi: 10.1038/onc.2016.7. Epub 2016 Feb 15.
• [22] The PDGFR/ERK1/2 pathway regulates CDCP1 expression in triple-negative breast cancer.BMC Cancer. 2018 May 23;18(1):586. doi: 10.1186/s12885-018-4500-9.
• [23] Expression of CUB domain containing protein (CDCP1) is correlated with prognosis and survival of patients with adenocarcinoma of lung.Cancer Sci. 2009 Mar;100(3):429-33. doi: 10.1111/j.1349-7006.2008.01066.x. Epub 2008 Dec 11.
• [24] Dynamic m(6)A mRNA methylation reveals the role of METTL3-m(6)A-CDCP1 signaling axis in chemical carcinogenesis.Oncogene. 2019 Jun;38(24):4755-4772. doi: 10.1038/s41388-019-0755-0. Epub 2019 Feb 22.
• [25] CUB Domain-containing Protein 1 (CDCP1) Is Down-regulated by Active Hexose-correlated Compound in Human Pancreatic Cancer Cells.Anticancer Res. 2018 Nov;38(11):6107-6111. doi: 10.21873/anticanres.12961.
• [26] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [27] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [28] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [29] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [30] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [31] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [32] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [33] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [34] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [35] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [36] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [37] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [38] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [39] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [40] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [41] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.