Oncotarget

Research Papers:

Repression of YAP by NCTD disrupts NSCLC progression

Jiwei Guo, Yan Wu, Lijuan Yang, Jing Du, Kaikai Gong, Weiwei Chen, Juanjuan Dai, XueLin Li and Sichuan Xi _

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Oncotarget. 2017; 8:2307-2319. https://doi.org/10.18632/oncotarget.13668

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Abstract

Jiwei Guo1,*, Yan Wu1,*, Lijuan Yang1, Jing Du1, Kaikai Gong1, Weiwei Chen1, Juanjuan Dai1, XueLin Li1, Sichuan Xi1

1Cancer Research Institute, Binzhou Medical University Hospital, Binzhou 256603, P.R. China

*These authors contributed equally to this work

Correspondence to:

Sichuan Xi, email: [email protected]

Keywords: lung cancer, YAP, NCTD, EMT, cell cycle arrest

Received: August 17, 2016     Accepted: November 21, 2016     Published: November 26, 2016

ABSTRACT

The efficacy of available lung cancer therapeutic interference is significantly limited by various resistance mechanisms to those drugs. Activation of the oncogene YAP underlying the initiation, progression, and metastasis of lung cancer associates with poor prognosis and confers drug resistance against targeted therapy. In this study, we evaluated the specificity of norcantharidin (NCTD) in repressing YAP to inhibit non-small cell lung carcinoma (NSCLC) progression. Our study revealed that YAP signal pathways were aberrantly activated in lung cancer tissues and cells which rendered more proliferative and invasive phenotypes to human lung cancer cells. We confirmed that NCTD specifically repressed YAP signaling pathway to interfere the YAP-mediated non-small cell lung carcinoma progression and metastasis via arresting cell cycle, enhancing apoptosis and inducing senescence. We also found NCTD-mediated repression of YAP decreased epithelial-to-mesenchymal transition (EMT) and reduced the motile and invasive cellular phenotype in vitro via enhancing E-cadherin and decreasing fibronectin/vimentin. Mechanistic investigations revealed that NCTD transcriptionally downregulated YAP and post-translationally modulated the subcellular redistribution of YAP between nucleus and cytoplasm. Collectively, our results indicated that NCTD is a novel therapeutic drug candidate for NSCLC which specifically and sensitively target YAP signal pathway.


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