Details of Drug Off-Target (DOT)

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

• DOT Name: Disabled homolog 2 (DAB2)
• Synonyms: Adaptor molecule disabled-2; Differentially expressed in ovarian carcinoma 2; DOC-2; Differentially-expressed protein 2
• Gene Name: DAB2
• Related Disease:
  Breast neoplasm
  Carcinoma of esophagus
  Chronic renal failure
  Esophageal cancer
  Hyperglycemia
  Neoplasm of esophagus
  Adenocarcinoma
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Bladder cancer
  Breast cancer
  Colitis
  Colorectal carcinoma
  Endometrial cancer
  Endometrial carcinoma
  Gastric cancer
  Huntington disease
  Lung adenocarcinoma
  Lung neoplasm
  Matthew-Wood syndrome
  Nasopharyngeal carcinoma
  Nephropathy
  Non-small-cell lung cancer
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Stomach cancer
  Transitional cell carcinoma
  Type-1/2 diabetes
  Urinary bladder cancer
  Urinary bladder neoplasm
  Urothelial carcinoma
  Carcinoma
  Cervical carcinoma
  High blood pressure
  Lung cancer
  Lung carcinoma
  Metabolic acidosis
  Squamous cell carcinoma
  Bone osteosarcoma
  Breast carcinoma
  Choriocarcinoma
  Chronic kidney disease
  Hepatocellular carcinoma
  Myocardial infarction
  Osteosarcoma
• UniProt ID: DAB2_HUMAN
• PDB ID: 2LSW; 6O5O; 6OVF
• Pfam ID: PF21792 ; PF00640
• Sequence:
  MSNEVETSATNGQPDQQAAPKAPSKKEKKKGPEKTDEYLLARFKGDGVKYKAKLIGIDDV
  PDARGDKMSQDSMMKLKGMAAAGRSQGQHKQRIWVNISLSGIKIIDEKTGVIEHEHPVNK
  ISFIARDVTDNRAFGYVCGGEGQHQFFAIKTGQQAEPLVVDLKDLFQVIYNVKKKEEEKK
  KIEEASKAVENGSEALMILDDQTNKLKSGVDQMDLFGDMSTPPDLNSPTESKDILLVDLN
  SEIDTNQNSLRENPFLTNGITSCSLPRPTPQASFLPENAFSANLNFFPTPNPDPFRDDPF
  TQPDQSTPSSFDSLKSPDQKKENSSSSSTPLSNGPLNGDVDYFGQQFDQISNRTGKQEAQ
  AGPWPFSSSQTQPAVRTQNGVSEREQNGFSVKSSPNPFVGSPPKGLSIQNGVKQDLESSV
  QSSPHDSIAIIPPPQSTKPGRGRRTAKSSANDLLASDIFAPPVSEPSGQASPTGQPTALQ
  PNPLDLFKTSAPAPVGPLVGLGGVTVTLPQAGPWNTASLVFNQSPSMAPGAMMGGQPSGF
  SQPVIFGTSPAVSGWNQPSPFAASTPPPVPVVWGPSASVAPNAWSTTSPLGNPFQSNIFP
  APAVSTQPPSMHSSLLVTPPQPPPRAGPPKDISSDAFTALDPLGDKEIKDVKEMFKDFQL
  RQPPAVPARKGEQTSSGTLSAFASYFNSKVGIPQENADHDDFDANQLLNKINEPPKPAPR
  QVSLPVTKSTDNAFENPFFKDSFGSSQASVASSQPVSSEMYRDPFGNPFA
• Function: Adapter protein that functions as a clathrin-associated sorting protein (CLASP) required for clathrin-mediated endocytosis of selected cargo proteins. Can bind and assemble clathrin, and binds simultaneously to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and cargos containing non-phosphorylated NPXY internalization motifs, such as the LDL receptor, to recruit them to clathrin-coated pits. Can function in clathrin-mediated endocytosis independently of the AP-2 complex. Involved in endocytosis of integrin beta-1; this function seems to redundant with the AP-2 complex and seems to require DAB2 binding to endocytosis accessory EH domain-containing proteins such as EPS15, EPS15L1 and ITSN1. Involved in endocytosis of cystic fibrosis transmembrane conductance regulator/CFTR. Involved in endocytosis of megalin/LRP2 lipoprotein receptor during embryonal development. Required for recycling of the TGF-beta receptor. Involved in CFTR trafficking to the late endosome. Involved in several receptor-mediated signaling pathways. Involved in TGF-beta receptor signaling and facilitates phosphorylation of the signal transducer SMAD2. Mediates TFG-beta-stimulated JNK activation. May inhibit the canoniocal Wnt/beta-catenin signaling pathway by stabilizing the beta-catenin destruction complex through a competing association with axin preventing its dephosphorylation through protein phosphatase 1 (PP1). Sequesters LRP6 towards clathrin-mediated endocytosis, leading to inhibition of Wnt/beta-catenin signaling. May activate non-canonical Wnt signaling. In cell surface growth factor/Ras signaling pathways proposed to inhibit ERK activation by interrupting the binding of GRB2 to SOS1 and to inhibit SRC by preventing its activating phosphorylation at 'Tyr-419'. Proposed to be involved in modulation of androgen receptor (AR) signaling mediated by SRC activation; seems to compete with AR for interaction with SRC. Plays a role in the CSF-1 signal transduction pathway. Plays a role in cellular differentiation. Involved in cell positioning and formation of visceral endoderm (VE) during embryogenesis and proposed to be required in the VE to respond to Nodal signaling coming from the epiblast. Required for the epithelial to mesenchymal transition, a process necessary for proper embryonic development. May be involved in myeloid cell differentiation and can induce macrophage adhesion and spreading. May act as a tumor suppressor.
• Tissue Specificity: Expressed in deep invaginations, inclusion cysts and the surface epithelial cells of the ovary. Also expressed in breast epithelial cells, spleen, thymus, prostate, testis, macrophages, fibroblasts, lung epithelial cells, placenta, brain stem, heart and small intestine. Expressed in kidney proximal tubular epithelial cells (at protein level).
• KEGG Pathway: Endocytosis (hsa04144)
• Reactome Pathway:
  Formation of annular gap junctions (R-HSA-196025)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Gap junction degradation (R-HSA-190873)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast neoplasm	DISNGJLM	Definitive	Biomarker	[1]
Carcinoma of esophagus	DISS6G4D	Definitive	Altered Expression	[2]
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[3]
Esophageal cancer	DISGB2VN	Definitive	Altered Expression	[2]
Hyperglycemia	DIS0BZB5	Definitive	Altered Expression	[4]
Neoplasm of esophagus	DISOLKAQ	Definitive	Altered Expression	[2]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[6]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[6]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Colitis	DISAF7DD	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[9]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[10]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[10]
Gastric cancer	DISXGOUK	Strong	Biomarker	[11]
Huntington disease	DISQPLA4	Strong	Altered Expression	[12]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[13]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[14]
Matthew-Wood syndrome	DISA7HR7	Strong	Altered Expression	[15]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[16]
Nephropathy	DISXWP4P	Strong	Biomarker	[17]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Posttranslational Modification	[18]
Pancreatic cancer	DISJC981	Strong	Biomarker	[15]
Prostate cancer	DISF190Y	Strong	Biomarker	[19]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[19]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[20]
Stomach cancer	DISKIJSX	Strong	Biomarker	[11]
Transitional cell carcinoma	DISWVVDR	Strong	Altered Expression	[21]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[22]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[7]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[7]
Urothelial carcinoma	DISRTNTN	Strong	Altered Expression	[21]
Carcinoma	DISH9F1N	moderate	Posttranslational Modification	[23]
Cervical carcinoma	DIST4S00	moderate	Biomarker	[24]
High blood pressure	DISY2OHH	moderate	Biomarker	[25]
Lung cancer	DISCM4YA	moderate	Biomarker	[26]
Lung carcinoma	DISTR26C	moderate	Biomarker	[26]
Metabolic acidosis	DIS7UMEC	moderate	Biomarker	[27]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[28]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[29]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[1]
Choriocarcinoma	DISDBVNL	Limited	Biomarker	[30]
Chronic kidney disease	DISW82R7	Limited	Biomarker	[17]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[31]
Myocardial infarction	DIS655KI	Limited	Biomarker	[32]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[29]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Disabled homolog 2 (DAB2) decreases the response to substance of Cisplatin.	[60]
Etoposide	DMNH3PG	Approved	Disabled homolog 2 (DAB2) affects the response to substance of Etoposide.	[61]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Disabled homolog 2 (DAB2).	[33]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Disabled homolog 2 (DAB2).	[34]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Disabled homolog 2 (DAB2).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Disabled homolog 2 (DAB2).	[36]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Disabled homolog 2 (DAB2).	[37]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Disabled homolog 2 (DAB2).	[38]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Disabled homolog 2 (DAB2).	[39]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Disabled homolog 2 (DAB2).	[40]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Disabled homolog 2 (DAB2).	[41]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Disabled homolog 2 (DAB2).	[42]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Disabled homolog 2 (DAB2).	[43]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Disabled homolog 2 (DAB2).	[44]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Disabled homolog 2 (DAB2).	[45]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Disabled homolog 2 (DAB2).	[46]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Disabled homolog 2 (DAB2).	[47]
Exemestane	DM9HPW3	Approved	Exemestane increases the expression of Disabled homolog 2 (DAB2).	[48]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Disabled homolog 2 (DAB2).	[49]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Disabled homolog 2 (DAB2).	[51]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Disabled homolog 2 (DAB2).	[52]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Disabled homolog 2 (DAB2).	[53]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Disabled homolog 2 (DAB2).	[56]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Disabled homolog 2 (DAB2).	[57]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Disabled homolog 2 (DAB2).	[58]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Avastin+/-Tarceva	DMA86FL	Phase 3	Avastin+/-Tarceva affects the phosphorylation of Disabled homolog 2 (DAB2).	[50]
R-roscovitine	DMSH108	Phase 2	R-roscovitine decreases the phosphorylation of Disabled homolog 2 (DAB2).	[50]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Disabled homolog 2 (DAB2).	[54]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Disabled homolog 2 (DAB2).	[55]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Disabled homolog 2 (DAB2).	[59]
Okadaic acid	DM47CO1	Investigative	Okadaic acid affects the phosphorylation of Disabled homolog 2 (DAB2).	[50]

References

• [1] miR-191/DAB2 axis regulates the tumorigenicity of estrogen receptor-positive breast cancer.IUBMB Life. 2018 Jan;70(1):71-80. doi: 10.1002/iub.1705. Epub 2017 Dec 16.
• [2] Loss of disabled-2 expression is an early event in esophageal squamous tumorigenesis.World J Gastroenterol. 2006 Oct 7;12(37):6041-5. doi: 10.3748/wjg.v12.i37.6041.
• [3] A catalog of genetic loci associated with kidney function from analyses of a million individuals.Nat Genet. 2019 Jun;51(6):957-972. doi: 10.1038/s41588-019-0407-x. Epub 2019 May 31.
• [4] MicroRNA-145 regulates disabled-2 and Wnt3a expression in cardiomyocytes under hyperglycaemia.Eur J Clin Invest. 2018 Jan;48(1). doi: 10.1111/eci.12867. Epub 2017 Dec 8.
• [5] Identification of DAB2 and Intelectin-1 as Novel Positive Immunohistochemical Markers of Epithelioid Mesothelioma by Transcriptome Microarray Analysis for Its Differentiation From Pulmonary Adenocarcinoma.Am J Surg Pathol. 2017 Aug;41(8):1045-1052. doi: 10.1097/PAS.0000000000000852.
• [6] Deficiency of Dab2 (Disabled Homolog 2) in Myeloid Cells Exacerbates Inflammation in Liver and Atherosclerotic Plaques in LDLR (Low-Density Lipoprotein Receptor)-Null Mice-Brief Report.Arterioscler Thromb Vasc Biol. 2018 May;38(5):1020-1029. doi: 10.1161/ATVBAHA.117.310467. Epub 2018 Mar 29.
• [7] Estrogen receptor promotes bladder cancer growth and invasion via alteration of miR-92a/DAB2IP signals.Exp Mol Med. 2018 Nov 20;50(11):1-11. doi: 10.1038/s12276-018-0155-5.
• [8] Rapid Downregulation of DAB2 by Toll-Like Receptor Activation Contributes to a Pro-Inflammatory Switch in Activated Dendritic Cells.Front Immunol. 2019 Feb 27;10:304. doi: 10.3389/fimmu.2019.00304. eCollection 2019.
• [9] DAB2IP with tumor-inhibiting activities exhibits frameshift mutations in gastrointestinal cancers.Pathol Res Pract. 2018 Dec;214(12):2075-2080. doi: 10.1016/j.prp.2018.10.005. Epub 2018 Oct 19.
• [10] Expression and clinical significance of the transforming growth factor- signalling pathway in endometrial cancer.Histopathology. 2011 Jul;59(1):63-72. doi: 10.1111/j.1365-2559.2011.03892.x.
• [11] Discovery of signature genes in gastric cancer associated with prognosis.Neoplasma. 2016;63(2):239-45. doi: 10.4149/209_150531N303.
• [12] Transcriptomics of maternal and fetal membranes can discriminate between gestational-age matched preterm neonates with and without cognitive impairment diagnosed at 18-24 months.PLoS One. 2015 Mar 30;10(3):e0118573. doi: 10.1371/journal.pone.0118573. eCollection 2015.
• [13] miR-134-5p Promotes Stage I Lung Adenocarcinoma Metastasis and Chemoresistance by Targeting DAB2.Mol Ther Nucleic Acids. 2019 Dec 6;18:627-637. doi: 10.1016/j.omtn.2019.09.025. Epub 2019 Oct 3.
• [14] miR-93-directed downregulation of DAB2 defines a novel oncogenic pathway in lung cancer.Oncogene. 2014 Aug 21;33(34):4307-15. doi: 10.1038/onc.2013.381. Epub 2013 Sep 16.
• [15] Loss of Disabled-2 Expression in Pancreatic Cancer Progression.Sci Rep. 2019 May 17;9(1):7532. doi: 10.1038/s41598-019-43992-z.
• [16] MicroRNA-93 promotes cell growth and invasion in nasopharyngeal carcinoma by targeting disabled homolog-2.Cancer Lett. 2015 Jul 28;363(2):146-55. doi: 10.1016/j.canlet.2015.04.006. Epub 2015 Apr 16.
• [17] Getting a Notch closer to renal dysfunction: activated Notch suppresses expression of the adaptor protein Disabled-2 in tubular epithelial cells.FASEB J. 2019 Jan;33(1):821-832. doi: 10.1096/fj.201800392RR. Epub 2018 Jul 27.
• [18] Aberrant Hypermethylation at Sites -86 to 226 of DAB2 Gene in Non-Small Cell Lung Cancer.Am J Med Sci. 2015 May;349(5):425-31. doi: 10.1097/MAJ.0000000000000436.
• [19] MiR-93 functions as a tumor promoter in prostate cancer by targeting disabled homolog 2 (DAB2) and an antitumor polysaccharide from green tea (Camellia sinensis) on their expression.Int J Biol Macromol. 2019 Mar 15;125:557-565. doi: 10.1016/j.ijbiomac.2018.12.088. Epub 2018 Dec 10.
• [20] The mechanism of growth-inhibitory effect of DOC-2/DAB2 in prostate cancer. Characterization of a novel GTPase-activating protein associated with N-terminal domain of DOC-2/DAB2.J Biol Chem. 2002 Apr 12;277(15):12622-31. doi: 10.1074/jbc.M110568200. Epub 2002 Jan 25.
• [21] Loss of DAB2IP expression in human urothelial carcinoma is associated with poorer recurrence-free survival.Virchows Arch. 2016 Jun;468(6):733-40. doi: 10.1007/s00428-016-1924-y. Epub 2016 Mar 22.
• [22] Mapping eGFR loci to the renal transcriptome and phenome in the VA Million Veteran Program.Nat Commun. 2019 Aug 26;10(1):3842. doi: 10.1038/s41467-019-11704-w.
• [23] Frequent methylation of DAB2, a Wnt pathway antagonist, in oral and oropharyngeal squamous cell carcinomas.Pathol Res Pract. 2018 Feb;214(2):314-317. doi: 10.1016/j.prp.2017.12.010. Epub 2017 Dec 14.
• [24] MicroRNA-106b is involved in transforming growth factor 1-induced cell migration by targeting disabled homolog 2 in cervical carcinoma.J Exp Clin Cancer Res. 2016 Jan 15;35:11. doi: 10.1186/s13046-016-0290-6.
• [25] Expression and Histopathological Significance of Disabled-2 in Aldosterone-Producing Adenoma.Horm Metab Res. 2017 Jul;49(7):520-526. doi: 10.1055/s-0043-100935. Epub 2017 May 17.
• [26] X-ray irradiation induced Disabled-2 gene promoter de-methylation enhances radiosensitivity of non-small-cell lung carcinoma cells.J Exp Clin Cancer Res. 2018 Dec 14;37(1):315. doi: 10.1186/s13046-018-1000-3.
• [27] Proteomic profiling of the effect of metabolic acidosis on the apical membrane of the proximal convoluted tubule.Am J Physiol Renal Physiol. 2012 Jun 1;302(11):F1465-77. doi: 10.1152/ajprenal.00390.2011. Epub 2012 Feb 22.
• [28] Epigenetic downregulation of human disabled homolog 2 switches TGF-beta from a tumor suppressor to a tumor promoter.J Clin Invest. 2010 Aug;120(8):2842-57. doi: 10.1172/JCI36125. Epub 2010 Jul 1.
• [29] Disabled homolog 2 interactive protein functions as a tumor suppressor in osteosarcoma cells.Oncol Lett. 2018 Jul;16(1):703-712. doi: 10.3892/ol.2018.8776. Epub 2018 May 22.
• [30] Doc-2/hDab2 expression is up-regulated in primary pancreatic cancer but reduced in metastasis.Lab Invest. 2001 Jun;81(6):863-73. doi: 10.1038/labinvest.3780295.
• [31] miR-106b targets DAB2 to promote hepatocellular carcinoma cell proliferation and metastasis.Oncol Lett. 2018 Sep;16(3):3063-3069. doi: 10.3892/ol.2018.8970. Epub 2018 Jun 15.
• [32] miR-145 is differentially regulated by TGF-1 and ischaemia and targets Disabled-2 expression and wnt/-catenin activity.J Cell Mol Med. 2012 May;16(5):1106-13. doi: 10.1111/j.1582-4934.2011.01385.x.
• [33] 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.
• [34] 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.
• [35] Constitutive gene expression predisposes morphogen-mediated cell fate responses of NT2/D1 and 27X-1 human embryonal carcinoma cells. Stem Cells. 2007 Mar;25(3):771-8. doi: 10.1634/stemcells.2006-0271. Epub 2006 Nov 30.
• [36] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [37] Evaluation of estrogen receptor alpha activation by glyphosate-based herbicide constituents. Food Chem Toxicol. 2017 Oct;108(Pt A):30-42.
• [38] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [39] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [40] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [41] 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.
• [42] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [43] 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.
• [44] Chronic ethanol exposure increases goosecoid (GSC) expression in human embryonic carcinoma cell differentiation. J Appl Toxicol. 2014 Jan;34(1):66-75.
• [45] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [46] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [47] Toxicoproteomics reveals an effect of clozapine on autophagy in human liver spheroids. Toxicol Mech Methods. 2023 Jun;33(5):401-410. doi: 10.1080/15376516.2022.2156005. Epub 2022 Dec 19.
• [48] Effects of aromatase inhibitors on human osteoblast and osteoblast-like cells: a possible androgenic bone protective effects induced by exemestane. Bone. 2007 Apr;40(4):876-87. doi: 10.1016/j.bone.2006.11.029. Epub 2006 Dec 28.
• [49] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [50] Cell cycle-dependent phosphorylation of Disabled-2 by cdc2. Oncogene. 2003 Jul 17;22(29):4524-30. doi: 10.1038/sj.onc.1206767.
• [51] Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. Cancer Res. 2006 Jul 15;66(14):7334-40.
• [52] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [53] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [54] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [55] 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.
• [56] 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.
• [57] 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.
• [58] The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.
• [59] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.
• [60] Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.
• [61] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.