Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5NWVP7)

• DOT Name: Krueppel-like factor 17 (KLF17)
• Synonyms: Zinc finger protein 393
• Gene Name: KLF17
• Related Disease:
  Breast neoplasm
  Cleft lip/palate
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Thyroid gland carcinoma
  Metastatic malignant neoplasm
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Carcinoma of esophagus
  Carcinoma of liver and intrahepatic biliary tract
  Colorectal carcinoma
  Esophageal cancer
  Liver cancer
  Lung adenocarcinoma
  Neoplasm of esophagus
  Thyroid gland papillary carcinoma
• UniProt ID: KLF17_HUMAN
• Pfam ID: PF00096
• Sequence:
  MYGRPQAEMEQEAGELSRWQAAHQAAQDNENSAPILNMSSSSGSSGVHTSWNQGLPSIQH
  FPHSAEMLGSPLVSVEAPGQNVNEGGPQFSMPLPERGMSYCPQATLTPSRMIYCQRMSPP
  QQEMTIFSGPQLMPVGEPNIPRVARPFGGNLRMPPNGLPVSASTGIPIMSHTGNPPVPYP
  GLSTVPSDETLLGPTVPSTEAQAVLPSMAQMLPPQDAHDLGMPPAESQSLLVLGSQDSLV
  SQPDSQEGPFLPEQPGPAPQTVEKNSRPQEGTGRRGSSEARPYCCNYENCGKAYTKRSHL
  VSHQRKHTGERPYSCNWESCSWSFFRSDELRRHMRVHTRYRPYKCDQCSREFMRSDHLKQ
  HQKTHRPGPSDPQANNNNGEQDSPPAAGP
• Function: Transcription repressor that binds to the promoter of target genes and prevents their expression. Acts as a negative regulator of epithelial-mesenchymal transition and metastasis in breast cancer. Specifically binds the 5'-CACCC-3' sequence in the promoter of ID1, a key metastasis regulator in breast cancer, and repress its expression. May be a germ cell-specific transcription factor that plays important roles in spermatid differentiation and oocyte development.

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast neoplasm	DISNGJLM	Strong	Biomarker	[1]
Cleft lip/palate	DIS14IG3	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Lung cancer	DISCM4YA	Strong	Biomarker	[4]
Lung carcinoma	DISTR26C	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[6]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[7]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[8]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[9]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[10]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[10]
Carcinoma of esophagus	DISS6G4D	Limited	Altered Expression	[9]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[11]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[5]
Esophageal cancer	DISGB2VN	Limited	Altered Expression	[9]
Liver cancer	DISDE4BI	Limited	Biomarker	[11]
Lung adenocarcinoma	DISD51WR	Limited	Biomarker	[4]
Neoplasm of esophagus	DISOLKAQ	Limited	Altered Expression	[9]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Altered Expression	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Krueppel-like factor 17 (KLF17).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Krueppel-like factor 17 (KLF17).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Krueppel-like factor 17 (KLF17).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Napabucasin	DMDZ6Q3	Phase 3	Napabucasin decreases the expression of Krueppel-like factor 17 (KLF17).	[13]
Fenfluramine	DM0762O	Phase 3	Fenfluramine increases the expression of Krueppel-like factor 17 (KLF17).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Krueppel-like factor 17 (KLF17).	[16]

References

• [1] ZNF652, a novel zinc finger protein, interacts with the putative breast tumor suppressor CBFA2T3 to repress transcription.Mol Cancer Res. 2006 Sep;4(9):655-65. doi: 10.1158/1541-7786.MCR-05-0249.
• [2] Irf6 directly regulates Klf17 in zebrafish periderm and Klf4 in murine oral epithelium, and dominant-negative KLF4 variants are present in patients with cleft lip and palate.Hum Mol Genet. 2016 Feb 15;25(4):766-76. doi: 10.1093/hmg/ddv614. Epub 2015 Dec 21.
• [3] Krppel-like factors in hepatocellular carcinoma.Tumour Biol. 2015 Feb;36(2):533-41. doi: 10.1007/s13277-015-3127-6. Epub 2015 Feb 6.
• [4] Krppel-like factor 17 inhibits urokinase plasminogen activator gene expression to suppress cell invasion through the Src/p38/ MAPK signaling pathway in human lung adenocarcionma.Oncotarget. 2017 Jun 13;8(24):38743-38754. doi: 10.18632/oncotarget.17020.
• [5] Clinical significance and biological role of KLF17 as a tumour suppressor in colorectal cancer.Oncol Rep. 2019 Nov;42(5):2117-2129. doi: 10.3892/or.2019.7324. Epub 2019 Sep 18.
• [6] Tumor-suppressive p53 Signaling Empowers Metastatic Inhibitor KLF17-dependent Transcription to Overcome Tumorigenesis in Non-small Cell Lung Cancer.J Biol Chem. 2015 Aug 28;290(35):21336-51. doi: 10.1074/jbc.M114.635730. Epub 2015 Apr 24.
• [7] RREB-1, a novel zinc finger protein, is involved in the differentiation response to Ras in human medullary thyroid carcinomas.Mol Cell Biol. 1996 Oct;16(10):5335-45. doi: 10.1128/MCB.16.10.5335.
• [8] Novel FUS-KLF17 and EWSR1-KLF17 fusions in myoepithelial tumors.Genes Chromosomes Cancer. 2015 May;54(5):267-75. doi: 10.1002/gcc.22240. Epub 2015 Feb 23.
• [9] Low expression of KLF17 is associated with tumor invasion in esophageal carcinoma.Int J Clin Exp Pathol. 2015 Sep 1;8(9):11157-63. eCollection 2015.
• [10] Low doses of Paclitaxel repress breast cancer invasion through DJ-1/KLF17 signalling pathway.Clin Exp Pharmacol Physiol. 2018 Apr 27. doi: 10.1111/1440-1681.12960. Online ahead of print.
• [11] Suppressed Krppellike factor 17 expression induces tumor proliferation, metastasis and a poor prognosis in papillary thyroid carcinoma.Mol Med Rep. 2014 Oct;10(4):2087-92. doi: 10.3892/mmr.2014.2429. Epub 2014 Jul 29.
• [12] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [13] Suppression of cancer relapse and metastasis by inhibiting cancer stemness. Proc Natl Acad Sci U S A. 2015 Feb 10;112(6):1839-44. doi: 10.1073/pnas.1424171112. Epub 2015 Jan 20.
• [14] Fenfluramine-induced gene dysregulation in human pulmonary artery smooth muscle and endothelial cells. Pulm Circ. 2011 Jul-Sep;1(3):405-18. doi: 10.4103/2045-8932.87310.
• [15] 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.
• [16] MCM5 as a target of BET inhibitors in thyroid cancer cells. Endocr Relat Cancer. 2016 Apr;23(4):335-47. doi: 10.1530/ERC-15-0322. Epub 2016 Feb 24.
• [17] 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.