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Title: Epithelial-mesenchymal transition as a potential route for DAPT resistance in breast cancer cells
Authors: Telli, Kübra
Yalçın Özuysal, Özden
Keywords: Breast cancer
Drug resistance
Notch signaling pathway
Publisher: Walter de Gruyter GmbH
Abstract: Notch is a conserved pathway involved in cell-fate determination and homeostasis. Its dysregulation plays a role in poor prognosis and drug resistance in breast cancer. Targeting Notch signaling via inhibition of the gamma-secretase complex is in the spotlight of modern cancer treatments. Gamma-secretase inhibitors (GSI) have shown successful clinical activity in treating cancers, yet the possible resistance mechanism remains unstudied. Modeling the resistance and understanding culprit molecular mechanisms can improve GSI therapies. Accordingly, the aim of this study is to generate and analyze GSI-resistant breast cancer cells. Gradually increasing doses of DAPT, a well-known GSI, were applied to MCF-7 breast cancer cell lines to generate resistance. Cell viability, migration and gene expressions were assessed by MTT, wound healing and qRT-PCR analyses. DAPT-resistant MCF-7 cells exhibited abnormal expression of Notch receptors, Notch targets (HES1, HES5, HEY1), and epithelial-mesenchymal transition (EMT) markers (E-cadherin, ZO-1, SNAIL2, N-cadherin) to overcome the continuous increase in DAPT toxicity by increased migration through mesenchymal transition. This study prospects into the role of EMT in the potential resistance mechanism against DAPT treatment for breast cancer cells. Complementary targeting of EMT should be investigated further for a possible effect to potentiate DAPT's anti-cancer effects.
ISSN: 0250-4685
Appears in Collections:Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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