The mRNA-edited form of GABRA3 suppresses GABRA3-mediated Akt activation and breast cancer metastasis

Kiranmai Gumireddy, Anping Li, Andrew V. Kossenkov, Masayuki Sakurai, Jinchun Yan, Yan Li, Hua Xu, Jian Wang, Paul J. Zhang, Lin Zhang, Louise C. Showe, Kazuko Nishikura and Qihong Huang ()
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Kiranmai Gumireddy: The Wistar Institute
Anping Li: The Wistar Institute
Andrew V. Kossenkov: The Wistar Institute
Masayuki Sakurai: The Wistar Institute
Jinchun Yan: University of Washington Medical Center
Yan Li: Institute of Cancer Stem Cell, College of Basic Medical Sciences, Dalian Medical University
Hua Xu: Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology
Jian Wang: Renji Hospital, Shanghai Jiao Tong University School of Medicine
Paul J. Zhang: Hospital of The University of Pennsylvania, Perelman School of Medicine
Lin Zhang: Perelman School of Medicine, University of Pennsylvania
Louise C. Showe: The Wistar Institute
Kazuko Nishikura: The Wistar Institute
Qihong Huang: The Wistar Institute

Nature Communications, 2016, vol. 7, issue 1, 1-9

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms10715

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