title: GABRA3 promotes lymphatic metastasis in lung adenocarcinoma by mediating upregulation of matrix metalloproteinases.
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.
authors.affiliation: The Translational Medicine Laboratory, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Liu
authors.affiliation: Southern Medical University, Guangzhou, China.|Department of Thoracic Surgery, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Chenglin
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Thoracic Surgery, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Shen
authors.affiliation: The Translational Medicine Laboratory, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Huang
authors.affiliation: The Translational Medicine Laboratory, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Weixuan
authors.initials: W
authors.lastname: Lin
authors.affiliation: The Translational Medicine Laboratory, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Hailing
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Thoracic Surgery, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Liang
authors.affiliation: Department of Thoracic Surgery, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Shao
authors.affiliation: The Translational Medicine Laboratory, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.|Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Department of Anesthesia, Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Southern Medical University, Guangzhou, China.|Department of Thoracic Surgery, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Jianxing
authors.initials: J
authors.lastname: He
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D000077192:Adenocarcinoma of Lung; D000818:Animals; D002465:Cell Movement; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D034622:RNA Interference; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation
chemical_list: C546257:GABRA3 protein, human; D011963:Receptors, GABA-A; D018808:Transcription Factor AP-1; D048031:JNK Mitogen-Activated Protein Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: GABRA3; JNK/AP-1; MMP; lymphatic metastasis; non-small cell lung cancer