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May 16, 2020SHILAP Revista de lepidopterología106 citationsOpen Access

Inhibition of Wnt/β-catenin pathway reverses multi-drug resistance and EMT in Oct4+/Nanog+ NSCLC cells

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LLLiyun LiuHZHongrui ZhuYLYahui Liao

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Abstract

Cancer drug resistance and epithelial-mesenchymal transition (EMT), a critical process of cancer invasion and metastasis, have recently been associated with the existence of cancer stem cells (CSCs). However, there are no appropriate CSC-markers of non-small cell lung cancer (NSCLC)-associated drug resistance and EMT. It is unknown if and how the drug-resistant and EMT phenotypes in NSCLC cells link to specific stemness-related pathways. Here, we found a significant elevated expression of both Oct4 and Nanog in gefitinib-resistant NSCLC cells, which displayed multi-drug resistance (MDR) properties and exhibited EMT phenotype. Ectopic co-expression of Oct4/Nanog empowered NSCLC cells with cancer stem cell properties, including self-renewal, drug resistance, EMT and high tumorigenic capacity. Following molecular mechanism investigation indicated Oct4/Nanog-regulated drug resistance and EMT change through Wnt/β-catenin signaling activation. Moreover, silencing β-catenin abrogated Oct4/Nanog-mediated MDR and EMT process in NSCLC cells. Our findings propose Wnt/β-catenin pathway as a promising therapeutic target for the treatment of progression and metastasis of NSCLC with CSC-like signatures and epithelial-mesenchymal transition phenotype.

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Liu et al. (2020) studied this question.

synapsesocial.com/papers/69df2b16d85e58e37b7a185chttps://doi.org/10.1016/j.biopha.2020.110225
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