Zinc finger RNA-binding protein promotes non-small-cell carcinoma growth and tumor metastasis by targeting the Notch signaling pathway.

ABSTRACT: Metastatic non-small-cell lung carcinoma (NSCLC) is typically incurable. The development of anti-metastatic therapies is hampered because the mechanisms regulating metastasis in NSCLC are not well known. Currently, there is no effective treatment for NSCLC once it has progressed to the metastatic stage. Therefore, further elucidation of the molecular mechanisms underlying the metastasis of NSCLC cells is urgently required for improving NSCLC treatment. Here, we report that the zinc finger RNA-binding protein (ZFR) is over-expressed in NSCLC cells and demonstrate that ZFR is a promising therapeutic target in metastatic NSCLC. The use of shRNA to knockdown ZFR impaired cell proliferation in vitro and tumor growth in vivo. Moreover, silencing of ZFR inhibited metastasis almost completely. In contrast, over-expression of ZFR in cells significantly enhanced NSCLC cell growth and metastasis. Finally, ZFR increased the metastatic potential of NSCLC cells in a Notch1-dependent manner. Collectively, our study reveals a critical role of ZFR in NSCLC tumor growth and metastasis, suggesting ZFR as a novel target for the treatment of NSCLC.

SUBMITTER: Zhang H 

PROVIDER: S-EPMC5622217 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature