Oncotarget

Research Papers:

A novel glutaminase inhibitor-968 inhibits the migration and proliferation of non-small cell lung cancer cells by targeting EGFR/ERK signaling pathway

Tianyu Han, Meng Guo, Tingting Zhang, Mingxi Gan, Caifeng Xie and Jian-Bin Wang _

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Oncotarget. 2017; 8:28063-28073. https://doi.org/10.18632/oncotarget.14188

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Abstract

Tianyu Han1,2,*, Meng Guo1,*, Tingting Zhang3, Mingxi Gan1, Caifeng Xie1, Jian-Bin Wang1

1Institute of Translational Medicine, Nanchang University, Nanchang City, Jiangxi 330031, China

2School of Life Sciences, Nanchang University, Nanchang City, Jiangxi 330031, China

3Research Institute of Applied Biology, Shanxi University, Taiyuan, Shanxi 030006, China

*These authors have contributed equally to this work

Correspondence to:

Jian-Bin Wang, email: jianbinwang1@gmail.com

Keywords: glutamine metabolism, glutaminase inhibitor, epidermal growth factor receptor, autophagy, non-small cell lung cancer

Received: August 04, 2016    Accepted: November 15, 2016    Published: December 26, 2016

ABSTRACT

Metabolic reprogramming is critical for cancer cell proliferation. Glutaminolysis which provides cancer cells with bioenergetics and intermediates for macromolecular synthesis have been intensively studied in recent years. Glutaminase C (GAC) is the first and rate-limiting enzyme in glutaminolysis and plays important roles in cancer initiation and progression. We previously screened a small molecule named 968, a specific inhibitor of GAC, to block the proliferation of human breast cancer cells. In this study, we found that 968 effectively inhibited NSCLC cell proliferation and migration and arrested G0/G1 phase of cell cycle. Furthermore, we demonstrated that 968 inhibited the EGFR/ERK pathway via decreasing the expression of EGFR and phospho-ERK. Apart from this, we discovered that 968 treatment induced autophagy to protect cells against apoptosis and the combination of 968 with autophagy inhibitor Chloroquine (CQ) had synergistic effects on the growth of NSCLC cells. Thus, our study pointed out a new therapeutic strategy for NSCLC treatment by combination of 968 with CQ.


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