Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik

Permanent URI for this collectionhttps://hdl.handle.net/11147/9

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Department: search.filters.department.Izmir Institute of TechnologyHas files: Yes

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  • Article
    Epithelial-Mesenchymal Transition as a Potential Route for Dapt Resistance in Breast Cancer Cells
    (Walter de Gruyter GmbH, 2023) Tellı, Kubra; Ozuysal, Ozden Yalcın; Telli, Kübra; Yalçın Özuysal, Özden
    Objectives: 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 treat- ments. Gamma-secretase inhibitors (GSI) have shown suc- cessful 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. Methods: 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. Results: 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. Conclusions: 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.
  • Review
    Citation - WoS: 19
    Citation - Scopus: 22
    Cancer Stem Cells in Tumor Modeling: Challenges and Future Directions
    (John Wiley and Sons Inc, 2021) Dogan,E.; Kisim,A.; Bati-Ayaz,G.; Kubicek,G.J.; Pesen-Okvur,D.; Miri,A.K.
    Microfluidic tumors-on-chips models have revolutionized anticancer therapeutic research by creating an ideal microenvironment for cancer cells. The tumor microenvironment (TME) includes various cell types and cancer stem cells (CSCs), which are postulated to regulate the growth, invasion, and migratory behavior of tumor cells. In this review, the biological niches of the TME and cancer cell behavior focusing on the behavior of CSCs are summarized. Conventional cancer models such as 3D cultures and organoid models are reviewed. Opportunities for the incorporation of CSCs with tumors-on-chips are then discussed for creating tumor invasion models. Such models will represent a paradigm shift in the cancer community by allowing oncologists and clinicians to predict better which cancer patients will benefit from chemotherapy treatments. © 2021 The Authors. Advanced NanoBiomed Research published by Wiley-VCH GmbH.