ZEB1 inhibition sensitizes cells to the ATR inhibitor VE-821 by abrogating epithelial–mesenchymal transition and enhancing DNA damage

References

• Yazinski SA, Zou L. Functions, regulation, and therapeutic implications of the ATR checkpoint pathway. Annu Rev Genet. 2016;50:155–173. doi:10.1146/annurev-genet-121415-121658. PMID:27617969
   PubMed Web of Science ®Google Scholar
• Karnitz LM, Zou L. Molecular pathways: targeting ATR in cancer therapy. Clin Cancer Res. 2015;21:4780–4785. doi:10.1158/1078-0432.CCR-15-0479. PMID:26362996
   PubMed Web of Science ®Google Scholar
• Abraham RT. Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev. 2001;15:2177–2196. doi:10.1101/gad.914401. PMID:11544175
   PubMed Web of Science ®Google Scholar
• Zou L. Single- and double-stranded DNA: building a trigger of ATR-mediated DNA damage response. Genes Dev. 2007;21:879–885. doi:10.1101/gad.1550307. PMID:17437994
   PubMed Web of Science ®Google Scholar
• Reaper PM, Griffiths MR, Long JM, et al. Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR. Nat Chem Biol. 2011;7:428–430. doi:10.1038/nchembio.573. PMID:21490603
   PubMed Web of Science ®Google Scholar
• Kim HJ, Min A, Im SA, et al. Anti-tumor activity of the ATR inhibitor AZD6738 in HER2 positive breast cancer cells. Int J Cancer. 2017;140:109–119.
   PubMed Web of Science ®Google Scholar
• Prevo R, Fokas E, Reaper PM, et al. The novel ATR inhibitor VE-821 increases sensitivity of pancreatic cancer cells to radiation and chemotherapy. Cancer Biol Ther. 2012;13:1072–1081. doi:10.4161/cbt.21093. PMID:22825331
   PubMed Web of Science ®Google Scholar
• Fokas E, Prevo R, Pollard JR, et al. Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation. Cell Death Dis. 2012;3:e441. doi:10.1038/cddis.2012.181. PMID:23222511
   PubMed Web of Science ®Google Scholar
• Jossé R, Martin SE, Guha R, et al. ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase i inhibitors by disabling DNA replication initiation and fork elongation responses. Cancer Res. 2014;74:6968–6979. doi:10.1158/0008-5472.CAN-13-3369. PMID:25269479
   PubMed Web of Science ®Google Scholar
• Min A, Im SA, Jang H, et al. AZD6738, a novel oral inhibitor of ATR, induces synthetic lethality with ATM deficiency in gastric cancer cells. Mol Cancer Ther. 2017;16:566–577. doi:10.1158/1535-7163.MCT-16-0378. PMID:28138034
   PubMed Web of Science ®Google Scholar
• Krajewska M, Fehrmann RS, Schoonen PM, et al. ATR inhibition preferentially targets homologous recombination-deficient tumor cells. Oncogene. 2015;34:3474–3481. doi:10.1038/onc.2014.276. PMID:25174396
   PubMed Web of Science ®Google Scholar
• Mitra A, Mishra L, Li S. EMT, CTCs and CSCs in tumor relapse and drug-resistance. Oncotarget. 2015;6:10697–10711. doi:10.18632/oncotarget.4037. PMID:25986923
   PubMed Web of Science ®Google Scholar
• Chang L, Graham PH, Hao J, et al. Acquisition of epithelial-mesenchymal transition and cancer stem cell phenotypes is associated with activation of the PI3K/Akt/mTOR pathway in prostate cancer radioresistance. Cell Death Dis. 2013;4:e875. doi:10.1038/cddis.2013.407. PMID:24157869
   PubMed Web of Science ®Google Scholar
• Zhang P, Sun Y, Ma L. ZEB1: at the crossroads of epithelial-mesenchymal transition, metastasis and therapy resistance. Cell Cycle. 2015;14:481–487. doi:10.1080/15384101.2015.1006048. PMID:25607528
   PubMed Web of Science ®Google Scholar
• Wang C, Jin H, Wang N, et al. Gas6/Axl Axis contributes to chemoresistance and metastasis in breast cancer through Akt/GSK-3β/β-catenin signaling. Theranostics. 2016;6:1205–1219. doi:10.7150/thno.15083. PMID:27279912
   PubMed Web of Science ®Google Scholar
• Zou J, Liu L, Wang Q, et al. Downregulation of miR-429 contributes to the development of drug resistance in epithelial ovarian cancer by targeting ZEB1. Am J Transl Res. 2017;9:1357–1368. PMID:28386361
   PubMed Web of Science ®Google Scholar
• Zhou G, Zhang F, Guo Y, et al. miR-200c enhances sensitivity of drug-resistant non-small cell lung cancer to gefitinib by suppression of PI3K/Akt signaling pathway and inhibites cell migration via targeting ZEB1. Biomed Pharmacother. 2017;85:113–119. doi:10.1016/j.biopha.2016.11.100. PMID:27930974
   PubMed Web of Science ®Google Scholar
• Li H, Xu L, Li C, et al. Ubiquitin ligase Cbl-b represses IGF-I-induced epithelial mesenchymal transition via ZEB2 and microRNA-200c regulation in gastric cancer cells. Mol Cancer. 2014;13:136. doi:10.1186/1476-4598-13-136. PMID:24885194
   PubMed Web of Science ®Google Scholar
• Xu L, Zhang Y, Qu X, E3 Ubiquitin ligase Cbl-b prevents tumor metastasis by maintaining the epithelial phenotype in multiple drug-resistant gastric and breast cancer cells. Neoplasia. 2017;19:374–382. doi:10.1016/j.neo.2017.01.011. PMID:28334634
   PubMed Web of Science ®Google Scholar
• Guo Y, Lang X, Lu Z, et al. MiR-10b directly targets ZEB1 and PIK3CA to curb adenomyotic epithelial cell invasiveness via upregulation of E-Cadherin and inhibition of Akt phosphorylation. Cell Physiol Biochem. 2015;35:2169–2180. doi:10.1159/000374022. PMID:25896413
   PubMed Web of Science ®Google Scholar
• Zhang P, Wei Y, Wang L, et al. ATM-mediated stabilization of ZEB1 promotes DNA damage response and radioresistance through CHK1. Nat Cell Biol. 2014;16:864–875. doi:10.1038/ncb3013. PMID:25086746
   PubMed Web of Science ®Google Scholar
• Sayan AE, Griffiths TR, Pal R, et al. SIP1 protein protects cells from DNA damage-induced apoptosis and has independent prognostic value in bladder cancer. Proc Natl Acad Sci U S A. 2009;106:14884–14889. doi:10.1073/pnas.0902042106. PMID:19706487
   PubMed Web of Science ®Google Scholar
• Song N, Liu S, Zhang J, et al. Cetuximab-induced MET activation acts as a novel resistance mechanism in colon cancer cells. Int J Mol Sci. 2014;15:5838–5851. doi:10.3390/ijms15045838. PMID:24714091
   PubMed Web of Science ®Google Scholar