STUDYING EFFECTS OF ZEB1 KO IN TRIPLE-NEGATIVE BREAST CANCER CELLS MDA-MB-231

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dc.contributor.authorIssakhanov, Darkhan
dc.date.accessioned2024-06-25T07:29:34Z
dc.date.available2024-06-25T07:29:34Z
dc.date.issued2024-04-26
dc.description.abstractOne of the main problems in cancer therapy is the resistance of cancer cells to various anticancer drugs. Targeted anticancer drugs categorized on their effect to cancer hallmarks. According to the principles of functioning, anticancer drugs are divided into: growth factor inhibitors, pro-apoptotic drugs, immune checkpoint inhibitors, telomerase inhibitors, inhibitors of VEGF signaling, PARP inhibitors, metastasis suppressors, inhibitors of glycolysis and aerobic metabolism, inactivators of drug efflux and detoxication machinery etc (Dembic, 2020). The main mechanisms of resistance to them are: increased DNA repair, increased efflux of drugs, enhanced metabolism of drugs, growth factor compensation, genetic and epigenetic factors modification (Holohan et al., 2013; Kachalaki et al., 2016; Mansoori et al., 2017). One of these mechanisms which helps to avoid drugs effect is epithelial-mesenchymal transition (EMT) (Hashemi et al., 2022). EMT can give resistance to such drugs as doxorubicin via AMPK overexpression (Andugulapati et al., 2022), cisplatin via 14,15-epoxyeicosatrienoic acid (Luo et al., 2018), tamoxifen via Cx43 loss (Wu et al., 2021) etc. Also EMT is activated for metastasis of cancer cells and as a result, unfavorable prognosis in treatment. That’s why EMT has particular importance in treating of triple-negative breast cancer (TNBC) (Grasset et al., 2022) the most aggressive type of breast cancer. TNBC is characterized by high heterogeneity and the absence of major target receptors: estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Many research groups reported about mesenchymal gene expression in TNBC, suggesting EMT (Jang et al., 2015). One of the regulators of EMT are Zinc finger E-Box binding homeobox 1 (ZEB1), proteins that encoded by ZEB1 gene, located on chromosome 10p11.2 (Williams et al., 1992). Main function of this transcription factor is linked to the promotor region of the epithelial cell marker protein E-cadherin, causing the cells to lose their epithelial properties (Larsen et al., 2016). The importance of ZEB1 in TNBC therapy is due to its ability to promote chemoresistance through various mechanisms such as activated ataxia-telangiectasia mutated (ATM) kinase expression by forming a ZEB1/p300/PCAF complex (X. Zhang et al., 2018) or by repression of E-cadherin in AR-negative docetaxel-resistant sublines (Hanrahan et al., 2017). This work shows the effect of a knockout of the gene responsible for the synthesis of ZEB1 using the CRISPR-CAS-9 technology.en_US
dc.identifier.citationIssakhanov, D. (2024). Studying effects of ZEB1 KO in triple-negative breast cancer cells MDA-MB-231. Nazarbayev University School of Medicineen_US
dc.identifier.urihttp://nur.nu.edu.kz/handle/123456789/7999
dc.language.isoenen_US
dc.publisherNazarbayev University School of Medicineen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subjectType of access: Restricteden_US
dc.subjectTriple-negative breast canceren_US
dc.subjectepithelial-mesenchymal transition (EMT)en_US
dc.subjectmesenchymal-epithelial transformation (MET)en_US
dc.subjectZinc finger E-Box binding homeobox 1 (ZEB1)en_US
dc.subjectCRISPR-Cas-9en_US
dc.titleSTUDYING EFFECTS OF ZEB1 KO IN TRIPLE-NEGATIVE BREAST CANCER CELLS MDA-MB-231en_US
dc.typeMaster's thesisen_US
workflow.import.sourcescience

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