title: The mRNA-edited form of GABRA3 suppresses GABRA3-mediated Akt activation and breast cancer metastasis.
abstract: Metastasis is a critical event affecting breast cancer patient survival. To identify molecules contributing to the metastatic process, we analysed The Cancer Genome Atlas (TCGA) breast cancer data and identified 41 genes whose expression is inversely correlated with survival. Here we show that GABAA receptor alpha3 (Gabra3), normally exclusively expressed in adult brain, is also expressed in breast cancer, with high expression of Gabra3 being inversely correlated with breast cancer survival. We demonstrate that Gabra3 activates the AKT pathway to promote breast cancer cell migration, invasion and metastasis. Importantly, we find an A-to-I RNA-edited form of Gabra3 only in non-invasive breast cancers and show that edited Gabra3 suppresses breast cancer cell invasion and metastasis. A-to-I-edited Gabra3 has reduced cell surface expression and suppresses the activation of AKT required for cell migration and invasion. Our study demonstrates a significant role for mRNA-edited Gabra3 in breast cancer metastasis.
authors: Department of Tumor Microenvironment and Metastasis, The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
authors: Kiranmai
authors: K
authors: Gumireddy
authors: Department of Tumor Microenvironment and Metastasis, The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
authors: Anping
authors: A
authors: Li
authors: Department of Tumor Microenvironment and Metastasis, The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
authors: Andrew V
authors: AV
authors: Kossenkov
authors: Department of Tumor Microenvironment and Metastasis, The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
authors: Masayuki
authors: M
authors: Sakurai
authors: University of Washington Medical Center, 1959 N.E. Pacific Street, Seattle, Washington 98195, USA.|Department of Radiation Oncology, Cancer Hospital of Fudan University, 270 Dong An Road, Shanghai 200032, China.
authors: Jinchun
authors: J
authors: Yan
authors: Institute of Cancer Stem Cell, Department of Anatomy, College of Basic Medical Sciences, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, China.
authors: Yan
authors: Y
authors: Li
authors: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan 430030, China.
authors: Hua
authors: H
authors: Xu
authors: Department of Biliary-Pancreatic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
authors: Jian
authors: J
authors: Wang
authors: Department of Pathology and Laboratory Medicine, Hospital of The University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors: Paul J
authors: PJ
authors: Zhang
authors: Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors: Lin
authors: L
authors: Zhang
authors: Department of Tumor Microenvironment and Metastasis, The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
authors: Louise C
authors: LC
authors: Showe
authors: Department of Tumor Microenvironment and Metastasis, The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
authors: Kazuko
authors: K
authors: Nishikura
authors: Department of Tumor Microenvironment and Metastasis, The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
authors: Qihong
authors: Q
authors: Huang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D016016:Proportional Hazards Models; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017393:RNA Editing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism
chemical_list: C546257:GABRA3 protein, human; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D051057:Proto-Oncogene Proteins c-akt