Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS75IGC)

• DOT Name: CKLF-like MARVEL transmembrane domain-containing protein 3 (CMTM3)
• Synonyms: Chemokine-like factor superfamily member 3
• Gene Name: CMTM3
• Related Disease:
  Adult glioblastoma
  Colorectal neoplasm
  Esophageal squamous cell carcinoma
  Gastric cancer
  Glioblastoma multiforme
  Neoplasm
  Advanced cancer
  Carcinoma
  Hepatocellular carcinoma
  Laryngeal squamous cell carcinoma
  Metastatic malignant neoplasm
  Squamous cell carcinoma
  Prostate cancer
  Prostate carcinoma
  Stomach cancer
• UniProt ID: CKLF3_HUMAN
• Pfam ID: PF01284
• Sequence:
  MWPPDPDPDPDPEPAGGSRPGPAVPGLRALLPARAFLCSLKGRLLLAESGLSFITFICYV
  ASSASAFLTAPLLEFLLALYFLFADAMQLNDKWQGLCWPMMDFLRCVTAALIYFAISITA
  IAKYSDGASKAAGVFGFFATIVFATDFYLIFNDVAKFLKQGDSADETTAHKTEEENSDSD
  SD
• Tissue Specificity: Expressed in the leukocytes, placenta and testis.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[2]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[3]
Gastric cancer	DISXGOUK	Strong	Biomarker	[4]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[5]
Carcinoma	DISH9F1N	moderate	Biomarker	[6]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[7]
Laryngeal squamous cell carcinoma	DIS9UUVF	moderate	Genetic Variation	[8]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[9]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[10]
Prostate cancer	DISF190Y	Limited	Biomarker	[11]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[11]
Stomach cancer	DISKIJSX	Limited	Biomarker	[4]

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 CKLF-like MARVEL transmembrane domain-containing protein 3 (CMTM3).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of CKLF-like MARVEL transmembrane domain-containing protein 3 (CMTM3).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of CKLF-like MARVEL transmembrane domain-containing protein 3 (CMTM3).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of CKLF-like MARVEL transmembrane domain-containing protein 3 (CMTM3).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of CKLF-like MARVEL transmembrane domain-containing protein 3 (CMTM3).	[15]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of CKLF-like MARVEL transmembrane domain-containing protein 3 (CMTM3).	[16]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of CKLF-like MARVEL transmembrane domain-containing protein 3 (CMTM3).	[17]
Menadione	DMSJDTY	Approved	Menadione affects the expression of CKLF-like MARVEL transmembrane domain-containing protein 3 (CMTM3).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of CKLF-like MARVEL transmembrane domain-containing protein 3 (CMTM3).	[20]

References

• [1] Systematic investigation of CMTM family genes suggests relevance to glioblastoma pathogenesis and CMTM1 and CMTM3 as priority targets.Genes Chromosomes Cancer. 2015 Jul;54(7):433-43. doi: 10.1002/gcc.22255. Epub 2015 Apr 30.
• [2] CMTM3, located at the critical tumor suppressor locus 16q22.1, is silenced by CpG methylation in carcinomas and inhibits tumor cell growth through inducing apoptosis.Cancer Res. 2009 Jun 15;69(12):5194-201. doi: 10.1158/0008-5472.CAN-08-3694. Epub 2009 Jun 9.
• [3] Chemokine-like factor-like MARVEL transmembrane domain-containing 3 expression is associated with a favorable prognosis in esophageal squamous cell carcinoma.Oncol Lett. 2017 May;13(5):2982-2988. doi: 10.3892/ol.2017.5837. Epub 2017 Mar 10.
• [4] CMTM3 decreases EGFR expression and EGF-mediated tumorigenicity by promoting Rab5 activity in gastric cancer.Cancer Lett. 2017 Feb 1;386:77-86. doi: 10.1016/j.canlet.2016.11.015. Epub 2016 Nov 17.
• [5] miR-135b-5p promotes gastric cancer progression by targeting CMTM3.Int J Oncol. 2018 Feb;52(2):589-598. doi: 10.3892/ijo.2017.4222. Epub 2017 Dec 11.
• [6] CMTM3 inhibits human testicular cancer cell growth through inducing cell-cycle arrest and apoptosis.PLoS One. 2014 Feb 28;9(2):e88965. doi: 10.1371/journal.pone.0088965. eCollection 2014.
• [7] CKLF-Like MARVEL Transmembrane Domain-Containing Member 3 (CMTM3) Inhibits the Proliferation and Tumorigenisis in Hepatocellular Carcinoma Cells.Oncol Res. 2017 Jan 26;25(2):285-293. doi: 10.3727/096504016X14732523471442. Epub 2016 Sep 13.
• [8] Elevated methylation of CMTM3 promoter in the male laryngeal squamous cell carcinoma patients.Clin Biochem. 2016 Nov;49(16-17):1278-1282. doi: 10.1016/j.clinbiochem.2016.08.002. Epub 2016 Aug 10.
• [9] Knockdown of CMTM3 promotes metastasis of gastric cancer via the STAT3/Twist1/EMT signaling pathway.Oncotarget. 2016 May 17;7(20):29507-19. doi: 10.18632/oncotarget.8789.
• [10] CMTM3 inhibits cell growth and migration and predicts favorable survival in oral squamous cell carcinoma.Tumour Biol. 2015 Sep;36(10):7849-58. doi: 10.1007/s13277-015-3504-1. Epub 2015 May 7.
• [11] CMTM3 is reduced in prostate cancer and inhibits migration, invasion and growth of LNCaP cells.Clin Transl Oncol. 2015 Aug;17(8):632-9. doi: 10.1007/s12094-015-1288-9. Epub 2015 May 20.
• [12] 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.
• [13] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [14] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [15] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [16] Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1. J Appl Toxicol. 2023 Aug;43(8):1214-1224. doi: 10.1002/jat.4457. Epub 2023 Mar 11.
• [17] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [18] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [19] 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.
• [20] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.