GABRA3 promotes lymphatic metastasis in lung adenocarcinoma by mediating upregulation of matrix metalloproteinases
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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
Jianxing He, email: firstname.lastname@example.org
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
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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