Oncotarget

Research Papers:

GABRA3 promotes lymphatic metastasis in lung adenocarcinoma by mediating upregulation of matrix metalloproteinases

Liping Liu, Chenglin Yang, Jianfei Shen, Liyan Huang, Weixuan Lin, Hailing Tang, Wenhua Liang, Wenlong Shao, Haibo Zhang and Jianxing He _

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Oncotarget. 2016; 7:32341-32350. https://doi.org/10.18632/oncotarget.8700

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Abstract

Liping Liu1,*, Chenglin Yang2,3,*, Jianfei Shen3, Liyan Huang1, Weixuan Lin1, Hailing Tang1, Wenhua Liang3, Wenlong Shao3, Haibo Zhang1,4, Jianxing He2,3

1The Translational Medicine Laboratory, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

2Southern Medical University, Guangzhou, China

3Department of Thoracic Surgery, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

4Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, Department of Anesthesia, Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada

*These authors contributed equally to this work

Correspondence to:

Jianxing He, email: hejx@vip.163.com

Keywords: non-small cell lung cancer, GABRA3, MMP, JNK/AP-1, lymphatic metastasis

Received: August 19, 2015     Accepted: March 18, 2016     Published: April 11, 2016

ABSTRACT

Tumor metastasis is the main reason for the poor prognosis of lung cancer patients. The GABAA receptor subunit GABRA3 is reportedly upregulated in lung cancer. Herein, we show that high GABRA3 protein expression in lung adenocarcinoma correlated positively with disease stage, lymphatic metastasis status and poor patient survival. In addition, GABRA3 induced MMP-2 and MMP-9 expression through activation of the JNK/AP-1 signaling pathway, which enhanced lymphatic metastasis by lung adenocarcinoma both in vitro and in vivo. These results indicate that GABRA3 promotes lymph node metastasis and may thus be an effective therapeutic target for anticancer treatment.


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