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KLF4 promotes c-Met amplification-mediated gefitinib resistance in NSCLC.

KLF4 promotes c-Met amplification-mediated gefitinib resistance in NSCLC.
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Feng W, Xie Q, Liu S, Ji Y, Li C, Wang C, Jin L,


Feng W, Xie Q, Liu S, Ji Y, Li C, Wang C, Jin L, (click to view)

Feng W, Xie Q, Liu S, Ji Y, Li C, Wang C, Jin L,

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Cancer science 2018 04 06() doi 10.1111/cas.13601

Abstract

Gefitinib have been widely used in the first-line treatment of advanced EGFR-mutated non-small-cell lung cancer (NSCLC). However, many NSCLC patients will acquire resistance to gefitinib after 9-14 months of treatment. This study revealed that Krüppel-like factor 4 (KLF4) contributes to the formation of gefitinib resistance in c-Met overexpressing NSCLC cells. We observed that KLF4 was overexpressed in c-Met overexpressing NSCLC cells and tissues. Knockdown of KLF4 increased tumorigenic properties in gefitinib-resistant NSCLC cell lines without c-Met overexpression, but it reduced tumorigenic properties and increased gefitinib sensitivity in gefitinib-resistant NSCLC cells with c-Met overexpression, whereas overexpression of KLF4 reduced gefitinib sensitivity in gefitinib-sensitive NSCLC cells. Furthermore, Western blot analysis revealed that KLF4 contributed to the formation of gefitinib resistance in c-Met overexpressing NSCLC cells by inhibiting the expression of apoptosis-related proteins under gefitinib treatment and activating the c-Met/Akt signaling pathway by decreasing the inhibition of β-Catenin on phosphorylation of c-Met to prevent blockade by gefitinib. In summary, this study’s results suggest that KLF4 is a promising candidate molecular target for both prevention and therapy of NSCLC with c-Met overexpression. This article is protected by copyright. All rights reserved.

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