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

Author

Listed:
  • 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
    Cancer Hospital of Fudan University)

  • 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)

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.

Suggested Citation

  • 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 & Qihong Huang, 2016. "The mRNA-edited form of GABRA3 suppresses GABRA3-mediated Akt activation and breast cancer metastasis," Nature Communications, Nature, vol. 7(1), pages 1-9, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10715
    DOI: 10.1038/ncomms10715
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