Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTADU8JJ)

DOT Name CCN family member 5 (CCN5)
Synonyms Connective tissue growth factor-like protein; CTGF-L; Connective tissue growth factor-related protein 58; WNT1-inducible-signaling pathway protein 2; WISP-2
Gene Name CCN5
Related Disease
Arteriosclerosis ( )
Atherosclerosis ( )
Breast cancer ( )
Breast carcinoma ( )
Bronchopulmonary dysplasia ( )
Carcinoma of esophagus ( )
Cardiac failure ( )
Congestive heart failure ( )
Esophageal cancer ( )
Esophageal squamous cell carcinoma ( )
Insulinoma ( )
Leiomyoma ( )
Malignant peripheral nerve sheath tumor ( )
Metabolic disorder ( )
Metastatic malignant neoplasm ( )
Neoplasm of esophagus ( )
Neurofibromatosis type 1 ( )
Obesity ( )
Osteoarthritis ( )
Plexiform neurofibroma ( )
Pulmonary fibrosis ( )
Rheumatoid arthritis ( )
Triple negative breast cancer ( )
Uterine fibroids ( )
Gastric cancer ( )
Stomach cancer ( )
Estrogen-receptor positive breast cancer ( )
ACTH-independent macronodular adrenal hyperplasia 1 ( )
Adenocarcinoma ( )
Advanced cancer ( )
Breast adenocarcinoma ( )
Breast neoplasm ( )
Cardiomyopathy ( )
Ductal breast carcinoma in situ ( )
Hyperplasia ( )
Pancreatic adenocarcinoma ( )
Pancreatic cancer ( )
Type-1/2 diabetes ( )
UniProt ID
CCN5_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
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Pfam ID
PF00219 ; PF19035 ; PF00093
Sequence
MRGTPKTHLLAFSLLCLLSKVRTQLCPTPCTCPWPPPRCPLGVPLVLDGCGCCRVCARRL
GEPCDQLHVCDASQGLVCQPGAGPGGRGALCLLAEDDSSCEVNGRLYREGETFQPHCSIR
CRCEDGGFTCVPLCSEDVRLPSWDCPHPRRVEVLGKCCPEWVCGQGGGLGTQPLPAQGPQ
FSGLVSSLPPGVPCPEWSTAWGPCSTTCGLGMATRVSNQNRFCRLETQRRLCLSRPCPPS
RGRSPQNSAF
Function
May play an important role in modulating bone turnover. Promotes the adhesion of osteoblast cells and inhibits the binding of fibrinogen to integrin receptors. In addition, inhibits osteocalcin production.
Tissue Specificity Expressed in primary osteoblasts, fibroblasts, ovary, testes, and heart.

Molecular Interaction Atlas (MIA) of This DOT

38 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Arteriosclerosis DISK5QGC Strong Altered Expression [1]
Atherosclerosis DISMN9J3 Strong Altered Expression [1]
Breast cancer DIS7DPX1 Strong Biomarker [2]
Breast carcinoma DIS2UE88 Strong Biomarker [2]
Bronchopulmonary dysplasia DISO0BY5 Strong Biomarker [3]
Carcinoma of esophagus DISS6G4D Strong Altered Expression [4]
Cardiac failure DISDC067 Strong Biomarker [5]
Congestive heart failure DIS32MEA Strong Biomarker [5]
Esophageal cancer DISGB2VN Strong Altered Expression [4]
Esophageal squamous cell carcinoma DIS5N2GV Strong Altered Expression [4]
Insulinoma DISIU1JS Strong Biomarker [6]
Leiomyoma DISLDDFN Strong Biomarker [7]
Malignant peripheral nerve sheath tumor DIS0JTN6 Strong Altered Expression [8]
Metabolic disorder DIS71G5H Strong Biomarker [5]
Metastatic malignant neoplasm DIS86UK6 Strong Altered Expression [9]
Neoplasm of esophagus DISOLKAQ Strong Altered Expression [4]
Neurofibromatosis type 1 DIS53JH9 Strong Biomarker [8]
Obesity DIS47Y1K Strong Biomarker [5]
Osteoarthritis DIS05URM Strong Biomarker [10]
Plexiform neurofibroma DISW4XX7 Strong Altered Expression [8]
Pulmonary fibrosis DISQKVLA Strong Altered Expression [11]
Rheumatoid arthritis DISTSB4J Strong Altered Expression [12]
Triple negative breast cancer DISAMG6N Strong Biomarker [13]
Uterine fibroids DISBZRMJ Strong Altered Expression [7]
Gastric cancer DISXGOUK moderate Biomarker [14]
Stomach cancer DISKIJSX moderate Biomarker [14]
Estrogen-receptor positive breast cancer DIS1H502 Disputed Biomarker [15]
ACTH-independent macronodular adrenal hyperplasia 1 DISH2YV8 Limited Altered Expression [16]
Adenocarcinoma DIS3IHTY Limited Biomarker [17]
Advanced cancer DISAT1Z9 Limited Biomarker [18]
Breast adenocarcinoma DISMPHJ0 Limited Altered Expression [19]
Breast neoplasm DISNGJLM Limited Biomarker [20]
Cardiomyopathy DISUPZRG Limited Biomarker [21]
Ductal breast carcinoma in situ DISLCJY7 Limited Altered Expression [19]
Hyperplasia DISK4DFB Limited Altered Expression [16]
Pancreatic adenocarcinoma DISKHX7S Limited Biomarker [17]
Pancreatic cancer DISJC981 Limited Biomarker [22]
Type-1/2 diabetes DISIUHAP Limited Biomarker [21]
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⏷ Show the Full List of 38 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Arsenic trioxide DM61TA4 Approved CCN family member 5 (CCN5) decreases the response to substance of Arsenic trioxide. [37]
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21 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of CCN family member 5 (CCN5). [23]
Estradiol DMUNTE3 Approved Estradiol increases the expression of CCN family member 5 (CCN5). [24]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of CCN family member 5 (CCN5). [25]
Progesterone DMUY35B Approved Progesterone decreases the expression of CCN family member 5 (CCN5). [26]
Fulvestrant DM0YZC6 Approved Fulvestrant increases the expression of CCN family member 5 (CCN5). [27]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of CCN family member 5 (CCN5). [28]
Nicotine DMWX5CO Approved Nicotine increases the expression of CCN family member 5 (CCN5). [29]
Piroxicam DMTK234 Approved Piroxicam increases the expression of CCN family member 5 (CCN5). [30]
Prednisolone DMQ8FR2 Approved Prednisolone increases the expression of CCN family member 5 (CCN5). [30]
Methylprednisolone DM4BDON Approved Methylprednisolone increases the expression of CCN family member 5 (CCN5). [30]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of CCN family member 5 (CCN5). [31]
Flavonoid derivative 1 DMCQP0B Patented Flavonoid derivative 1 decreases the expression of CCN family member 5 (CCN5). [32]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of CCN family member 5 (CCN5). [31]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of CCN family member 5 (CCN5). [33]
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of CCN family member 5 (CCN5). [34]
Nickel chloride DMI12Y8 Investigative Nickel chloride increases the expression of CCN family member 5 (CCN5). [35]
Kaempferol DMHEMUB Investigative Kaempferol increases the expression of CCN family member 5 (CCN5). [31]
Apigenin DMI3491 Investigative Apigenin increases the expression of CCN family member 5 (CCN5). [31]
27-hydroxycholesterol DM2L6OZ Investigative 27-hydroxycholesterol increases the expression of CCN family member 5 (CCN5). [36]
N-nonylphenol DMH3OUX Investigative N-nonylphenol increases the expression of CCN family member 5 (CCN5). [31]
HPTE DMRPZD4 Investigative HPTE increases the expression of CCN family member 5 (CCN5). [31]
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⏷ Show the Full List of 21 Drug(s)

References

1 Aging differentially modulates the Wnt pro-survival signalling pathways in vascular smooth muscle cells.Aging Cell. 2019 Feb;18(1):e12844. doi: 10.1111/acel.12844. Epub 2018 Dec 12.
2 Deficiency of CCN5/WISP-2-Driven Program in breast cancer Promotes Cancer Epithelial cells to mesenchymal stem cells and Breast Cancer growth.Sci Rep. 2017 Apr 27;7(1):1220. doi: 10.1038/s41598-017-00916-z.
3 CCN5 in alveolar epithelial proliferation and differentiation during neonatal lung oxygen injury.J Cell Commun Signal. 2018 Mar;12(1):217-229. doi: 10.1007/s12079-017-0443-1. Epub 2018 Jan 18.
4 WISP2 exhibits its potential antitumor activity via targeting ERK and E-cadherin pathways in esophageal cancer cells.J Exp Clin Cancer Res. 2019 Feb 26;38(1):102. doi: 10.1186/s13046-019-1108-0.
5 CCN5/WISP2 and metabolic diseases.J Cell Commun Signal. 2018 Mar;12(1):309-318. doi: 10.1007/s12079-017-0437-z. Epub 2017 Dec 15.
6 Recombinant protein CCN5/WISP2 promotes islet cell proliferation and survival in vitro.Growth Factors. 2019 Aug;37(3-4):120-130. doi: 10.1080/08977194.2019.1652400. Epub 2019 Aug 22.
7 The growth arrest-specific gene CCN5 is deficient in human leiomyomas and inhibits the proliferation and motility of cultured human uterine smooth muscle cells.Mol Hum Reprod. 2004 Mar;10(3):181-7. doi: 10.1093/molehr/gah028. Epub 2004 Jan 29.
8 Differential expression of CCN1/CYR61, CCN3/NOV, CCN4/WISP1, and CCN5/WISP2 in neurofibromatosis type 1 tumorigenesis.J Neuropathol Exp Neurol. 2010 Jan;69(1):60-9. doi: 10.1097/NEN.0b013e3181c79bff.
9 Differential expression and prognostic implications of the CCN family members WISP-1, WISP-2, and WISP-3 in human breast cancer.Ann Surg Oncol. 2007 Jun;14(6):1909-18. doi: 10.1245/s10434-007-9376-x. Epub 2007 Apr 4.
10 Whole-transcriptome sequencing of knee joint cartilage from osteoarthritis patients.Bone Joint Res. 2019 Aug 2;8(7):290-303. doi: 10.1302/2046-3758.87.BJR-2018-0297.R1. eCollection 2019 Jul.
11 CCN5 overexpression inhibits profibrotic phenotypes via the PI3K/Akt signaling pathway in lung fibroblasts isolated from patients with idiopathic pulmonary fibrosis and in an in vivo model of lung fibrosis.Int J Mol Med. 2014 Feb;33(2):478-86. doi: 10.3892/ijmm.2013.1565. Epub 2013 Nov 25.
12 Expression profiles of human CCN genes in patients with osteoarthritis or rheumatoid arthritis.J Orthop Sci. 2015 Jul;20(4):708-16. doi: 10.1007/s00776-015-0727-3. Epub 2015 May 19.
13 CCN5/WISP-2 promotes growth arrest of triple-negative breast cancer cells through accumulation and trafficking of p27(Kip1) via Skp2 and FOXO3a regulation.Oncogene. 2015 Jun 11;34(24):3152-63. doi: 10.1038/onc.2014.250. Epub 2014 Aug 18.
14 Clinical Correlation Between WISP2 and -Catenin in Gastric Cancer.Anticancer Res. 2017 Aug;37(8):4469-4473. doi: 10.21873/anticanres.11842.
15 Loss of WISP2/CCN5 in estrogen-dependent MCF7 human breast cancer cells promotes a stem-like cell phenotype.PLoS One. 2014 Feb 3;9(2):e87878. doi: 10.1371/journal.pone.0087878. eCollection 2014.
16 Gene array analysis of macronodular adrenal hyperplasia confirms clinical heterogeneity and identifies several candidate genes as molecular mediators.Oncogene. 2004 Feb 26;23(8):1575-85. doi: 10.1038/sj.onc.1207277.
17 Loss of WISP-2/CCN5 signaling in human pancreatic cancer: a potential mechanism for epithelial-mesenchymal-transition.Cancer Lett. 2007 Aug 28;254(1):63-70. doi: 10.1016/j.canlet.2007.02.012. Epub 2007 Mar 26.
18 A role for WISP2 in colorectal cancer cell invasion and motility.Cancer Genomics Proteomics. 2013 Jul-Aug;10(4):187-96.
19 CCN5/WISP-2 expression in breast adenocarcinoma is associated with less frequent progression of the disease and suppresses the invasive phenotypes of tumor cells.Cancer Res. 2008 Sep 15;68(18):7606-12. doi: 10.1158/0008-5472.CAN-08-1461.
20 CCN5, a novel transcriptional repressor of the transforming growth factor signaling pathway.Mol Cell Biol. 2011 Apr;31(7):1459-69. doi: 10.1128/MCB.01316-10. Epub 2011 Jan 24.
21 CCN5 knockout mice exhibit lipotoxic cardiomyopathy with mild obesity and diabetes.PLoS One. 2018 Nov 28;13(11):e0207228. doi: 10.1371/journal.pone.0207228. eCollection 2018.
22 Detection of CCN1 and CCN5 mRNA in Human Cancer Samples Using a Modified In Situ Hybridization Technique.Methods Mol Biol. 2017;1489:495-504. doi: 10.1007/978-1-4939-6430-7_41.
23 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
24 WISP-2 as a novel estrogen-responsive gene in human breast cancer cells. Biochem Biophys Res Commun. 2000 Aug 18;275(1):108-14. doi: 10.1006/bbrc.2000.3276.
25 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
26 Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
27 Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
28 Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
29 Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
30 Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
31 Endocrine-Disrupting Chemicals (EDCs): In Vitro Mechanism of Estrogenic Activation and Differential Effects on ER Target Genes. Environ Health Perspect. 2013 Apr;121(4):459-66. doi: 10.1289/ehp.1205951. Epub 2013 Feb 5.
32 Cytotoxicity of flavones and flavonols to a human esophageal squamous cell carcinoma cell line (KYSE-510) by induction of G2/M arrest and apoptosis. Toxicol In Vitro. 2009 Aug;23(5):797-807. doi: 10.1016/j.tiv.2009.04.007. Epub 2009 May 3.
33 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
34 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.
35 Effects of nickel treatment on H3K4 trimethylation and gene expression. PLoS One. 2011 Mar 24;6(3):e17728. doi: 10.1371/journal.pone.0017728.
36 27-hydroxycholesterol is an endogenous selective estrogen receptor modulator. Mol Endocrinol. 2008 Jan;22(1):65-77. doi: 10.1210/me.2007-0383. Epub 2007 Sep 13.
37 The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.