Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQK2AMX)

• DOT Name: Tenascin-N (TNN)
• Synonyms: TN-N; Tenascin-W; TN-W
• Gene Name: TNN
• Related Disease:
  Adult glioblastoma
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colorectal neoplasm
  Glioblastoma multiforme
  Neoplasm
• UniProt ID: TENN_HUMAN
• Pfam ID: PF07974 ; PF18720 ; PF00147 ; PF00041
• Sequence:
  MSLQEMFRFPMGLLLGSVLLVASAPATLEPPGCSNKEQQVTVSHTYKIDVPKSALVQVDA
  DPQPLSDDGASLLALGEAREEQNIIFRHNIRLQTPQKDCELAGSVQDLLARVKKLEEEMV
  EMKEQCSAQRCCQGVTDLSRHCSGHGTFSLETCSCHCEEGREGPACERLACPGACSGHGR
  CVDGRCLCHEPYVGADCGYPACPENCSGHGECVRGVCQCHEDFMSEDCSEKRCPGDCSGH
  GFCDTGECYCEEGFTGLDCAQVVTPQGLQLLKNTEDSLLVSWEPSSQVDHYLLSYYPLGK
  ELSGKQIQVPKEQHSYEILGLLPGTKYIVTLRNVKNEVSSSPQHLLATTDLAVLGTAWVT
  DETENSLDVEWENPSTEVDYYKLRYGPMTGQEVAEVTVPKSSDPKSRYDITGLHPGTEYK
  ITVVPMRGELEGKPILLNGRTEIDSPTNVVTDRVTEDTATVSWDPVQAVIDKYVVRYTSA
  DGDTKEMAVHKDESSTVLTGLKPGEAYKVYVWAERGNQGSKKADTNALTEIDSPANLVTD
  RVTENTATISWDPVQATIDKYVVRYTSADDQETREVLVGKEQSSTVLTGLRPGVEYTVHV
  WAQKGDRESKKADTNAPTDIDSPKNLVTDRVTENMATVSWDPVQAAIDKYVVRYTSAGGE
  TREVPVGKEQSSTVLTGLRPGMEYMVHVWAQKGDQESKKADTKAQTDIDSPQNLVTDRVT
  ENMATVSWDPVRATIDRYVVRYTSAKDGETREVPVGKEQSSTVLTGLRPGVEYTVHVWAQ
  KGAQESKKADTKAQTDIDSPQNLVTDWVTENTATVSWDPVQATIDRYVVHYTSANGETRE
  VPVGKEQSSTVLTGLRPGMEYTVHVWAQKGNQESKKADTKAQTEIDGPKNLVTDWVTENM
  ATVSWDPVQATIDKYMVRYTSADGETREVPVGKEHSSTVLTGLRPGMEYMVHVWAQKGAQ
  ESKKADTKAQTELDPPRNLRPSAVTQSGGILTWTPPSAQIHGYILTYQFPDGTVKEMQLG
  REDQRFALQGLEQGATYPVSLVAFKGGRRSRNVSTTLSTVGARFPHPSDCSQVQQNSNAA
  SGLYTIYLHGDASRPLQVYCDMETDGGGWIVFQRRNTGQLDFFKRWRSYVEGFGDPMKEF
  WLGLDKLHNLTTGTPARYEVRVDLQTANESAYAIYDFFQVASSKERYKLTVGKYRGTAGD
  ALTYHNGWKFTTFDRDNDIALSNCALTHHGGWWYKNCHLANPNGRYGETKHSEGVNWEPW
  KGHEFSIPYVELKIRPHGYSREPVLGRKKRTLRGRLRTF
• Function: Extracellular matrix protein that seems to be a ligand for ITGA8:ITGB1, ITGAV:ITGB1 and ITGA4:ITGB1. Involved in neurite outgrowth and cell migration in hippocampal explants. During endochondral bone formation, inhibits proliferation and differentiation of proteoblasts mediated by canonical WNT signaling. In tumors, stimulates angiogenesis by elongation, migration and sprouting of endothelial cells. Expressed in most mammary tumors, may facilitate tumorigenesis by supporting the migratory behavior of breast cancer cells.
• Tissue Specificity: Not detected in normal adult mammary tissues or brain but expressed in most breast tumors and brain tumors, such as glioblastomas, astrocytomas and oligodendrogliomas, tested . In brain tumors, detected around the endothelial cell layer of the clood vessels .
• KEGG Pathway:
  PI3K-Akt sig.ling pathway (hsa04151)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Human papillomavirus infection (hsa05165)
  MicroR.s in cancer (hsa05206)
• Reactome Pathway: ECM proteoglycans (R-HSA-3000178)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[3]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[3]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Limited	Altered Expression	[4]

8 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 Tenascin-N (TNN).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Tenascin-N (TNN).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Tenascin-N (TNN).	[7]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Tenascin-N (TNN).	[7]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Tenascin-N (TNN).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Tenascin-N (TNN).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Tenascin-N (TNN).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Tenascin-N (TNN).	[11]

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 Tenascin-N (TNN).	[9]

References

• [1] Transcriptional regulation of tenascin-W by TGF-beta signaling in the bone metastatic niche of breast cancer cells.Int J Cancer. 2015 Oct 15;137(8):1842-54. doi: 10.1002/ijc.29565. Epub 2015 Apr 29.
• [2] Tenascins and the importance of adhesion modulation.Cold Spring Harb Perspect Biol. 2011 May 1;3(5):a004960. doi: 10.1101/cshperspect.a004960.
• [3] Tenascin-W, a new marker of cancer stroma, is elevated in sera of colon and breast cancer patients.Int J Cancer. 2008 Jun 1;122(11):2454-61. doi: 10.1002/ijc.23417.
• [4] The Expression and Possible Functions of Tenascin-W During Development and Disease.Front Cell Dev Biol. 2019 Apr 12;7:53. doi: 10.3389/fcell.2019.00053. eCollection 2019.
• [5] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [6] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [7] 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.
• [8] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [9] 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.
• [10] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.