Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVFJJ91)

• DOT Name: Protein S100-A14 (S100A14)
• Synonyms: S100 calcium-binding protein A14; S114
• Gene Name: S100A14
• Related Disease:
  Epithelial ovarian cancer
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Ovarian cancer
  Ovarian neoplasm
  Adenocarcinoma
  Breast cancer
  Carcinoma of esophagus
  Dermatitis
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Hepatocellular carcinoma
  Huntington disease
  Neoplasm
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Oral cancer
  Pancreatic adenocarcinoma
  Psoriasis
  Skin disease
  Squamous cell carcinoma
  Breast carcinoma
  Gastric cancer
  Oral cavity carcinoma
  Stomach cancer
  Advanced cancer
• UniProt ID: S10AE_HUMAN
• PDB ID: 2M0R
• Pfam ID: PF01023
• Sequence:
  MGQCRSANAEDAQEFSDVERAIETLIKNFHQYSVEGGKETLTPSELRDLVTQQLPHLMPS
  NCGLEEKIANLGSCNDSKLEFRSFWELIGEAAKSVKLERPVRGH
• Function: Modulates P53/TP53 protein levels, and thereby plays a role in the regulation of cell survival and apoptosis. Depending on the context, it can promote cell proliferation or apoptosis. Plays a role in the regulation of cell migration by modulating the levels of MMP2, a matrix protease that is under transcriptional control of P53/TP53. Does not bind calcium.
• Tissue Specificity: Expressed at highest levels in colon and at moderate levels in thymus, kidney, liver, small intestine, and lung. Low expression in heart and no expression is seen in brain, skeletal muscle, spleen, placenta and peripheral blood leukocytes.

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epithelial ovarian cancer	DIS56MH2	Definitive	Altered Expression	[1]
Lung adenocarcinoma	DISD51WR	Definitive	Altered Expression	[2]
Lung cancer	DISCM4YA	Definitive	Posttranslational Modification	[3]
Lung carcinoma	DISTR26C	Definitive	Posttranslational Modification	[3]
Ovarian cancer	DISZJHAP	Definitive	Biomarker	[1]
Ovarian neoplasm	DISEAFTY	Definitive	Biomarker	[1]
Adenocarcinoma	DIS3IHTY	Strong	Genetic Variation	[3]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[5]
Dermatitis	DISY5SZC	Strong	Genetic Variation	[6]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[5]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[8]
Huntington disease	DISQPLA4	Strong	Biomarker	[9]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Neoplasm of esophagus	DISOLKAQ	Strong	Altered Expression	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[10]
Oral cancer	DISLD42D	Strong	Genetic Variation	[11]
Pancreatic adenocarcinoma	DISKHX7S	Strong	Altered Expression	[12]
Psoriasis	DIS59VMN	Strong	Altered Expression	[6]
Skin disease	DISDW8R6	Strong	Altered Expression	[6]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[13]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[4]
Gastric cancer	DISXGOUK	moderate	Biomarker	[14]
Oral cavity carcinoma	DISZXMVL	moderate	Biomarker	[15]
Stomach cancer	DISKIJSX	moderate	Biomarker	[14]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[16]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Protein S100-A14 (S100A14) decreases the response to substance of Arsenic trioxide.	[28]

10 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 Protein S100-A14 (S100A14).	[17]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein S100-A14 (S100A14).	[18]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein S100-A14 (S100A14).	[19]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein S100-A14 (S100A14).	[20]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein S100-A14 (S100A14).	[21]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Protein S100-A14 (S100A14).	[22]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Protein S100-A14 (S100A14).	[23]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Protein S100-A14 (S100A14).	[24]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Protein S100-A14 (S100A14).	[25]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Protein S100-A14 (S100A14).	[27]

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 decreases the methylation of Protein S100-A14 (S100A14).	[26]

References

• [1] The role of S100A14 in epithelial ovarian tumors.Oncotarget. 2014 Jun 15;5(11):3482-96. doi: 10.18632/oncotarget.1947.
• [2] Overexpression of S100A14 contributes to malignant progression and predicts poor prognosis of lung adenocarcinoma.Thorac Cancer. 2018 Jul;9(7):827-835. doi: 10.1111/1759-7714.12654. Epub 2018 May 7.
• [3] Increased S100A15 expression and decreased DNA methylation of its gene promoter are involved in high metastasis potential and poor outcome of lung adenocarcinoma.Oncotarget. 2017 Jul 11;8(28):45710-45724. doi: 10.18632/oncotarget.17391.
• [4] Prognostic and clinicopathological significance of S100A14 expression in cancer patients: A meta-analysis.Medicine (Baltimore). 2019 Jul;98(28):e16356. doi: 10.1097/MD.0000000000016356.
• [5] S100A14: novel modulator of terminal differentiation in esophageal cancer.Mol Cancer Res. 2013 Dec;11(12):1542-53. doi: 10.1158/1541-7786.MCR-13-0317. Epub 2013 Oct 9.
• [6] Human S100A15 splice variants are differentially expressed in inflammatory skin diseases and regulated through Th1 cytokines and calcium.Exp Dermatol. 2007 Aug;16(8):685-91. doi: 10.1111/j.1600-0625.2007.00587.x.
• [7] S100A14 rs11548103 G>A polymorphism is associated with a decreased risk of esophageal cancer in a Chinese population.Oncotarget. 2017 Sep 14;8(49):86917-86923. doi: 10.18632/oncotarget.20868. eCollection 2017 Oct 17.
• [8] S100A14 promotes the growth and metastasis of hepatocellular carcinoma.Asian Pac J Cancer Prev. 2013;14(6):3831-6. doi: 10.7314/apjcp.2013.14.6.3831.
• [9] Mapping of D4S98/S114/S113 confines the Huntington's defect to a reduced physical region at the telomere of chromosome 4.Nucleic Acids Res. 1988 Dec 23;16(24):11769-80. doi: 10.1093/nar/16.24.11769.
• [10] Peripheral immune cell gene expression changes in advanced non-small cell lung cancer patients treated with first line combination chemotherapy.PLoS One. 2013;8(2):e57053. doi: 10.1371/journal.pone.0057053. Epub 2013 Feb 25.
• [11] Profiling of chromosomal changes in potentially malignant and malignant oral mucosal lesions from South and South-East Asia using array-comparative genomic hybridization.Cancer Genomics Proteomics. 2014 May-Jun;11(3):127-40.
• [12] Weighted Gene Co-Expression Network Analysis Reveals Six Hub Genes Involved in and Tight Junction Function in Pancreatic Adenocarcinoma and their Potential Use in Prognosis.Genet Test Mol Biomarkers. 2019 Dec;23(12):829-836. doi: 10.1089/gtmb.2019.0122.
• [13] Inflammation-mediated skin tumorigenesis induced by epidermal c-Fos.Genes Dev. 2013 Sep 15;27(18):1959-73. doi: 10.1101/gad.223339.113. Epub 2013 Sep 12.
• [14] Calcium-binding protein S100A14 induces differentiation and suppresses metastasis in gastric cancer.Cell Death Dis. 2017 Jul 20;8(7):e2938. doi: 10.1038/cddis.2017.297.
• [15] S100A14 inhibits proliferation of oral carcinoma derived cells through G1-arrest.Oral Oncol. 2012 Mar;48(3):219-25. doi: 10.1016/j.oraloncology.2011.10.001. Epub 2011 Oct 26.
• [16] Expression profile and functional role of S100A14 in human cancer.Oncotarget. 2019 Apr 26;10(31):2996-3012. doi: 10.18632/oncotarget.26861. eCollection 2019 Apr 26.
• [17] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [18] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [19] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [20] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [21] 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.
• [22] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [23] 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.
• [24] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [25] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [26] 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.
• [27] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [28] 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.