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 GABA(A) 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.
基金:
Doctors Cancer Foundation; Breast Cancer Alliance; W.W. Smith Foundation; Edward Mallinckrodt Jr Foundation; National Natural Science Funds [81372328, 81572834, R01-GM040536, R01-CA175058]; ACS-IRG [R01CA142776, R01CA190415]; Macular Vision Research Foundation; Cancer Center Support Grant (CCSG) [CA010815]; [R01CA148759]
第一作者单位:[1]Wistar Inst Anat & Biol, Dept Tumor Microenvironm & Metastasis, 3601 Spruce St, Philadelphia, PA 19104 USA
通讯作者:
推荐引用方式(GB/T 7714):
Gumireddy Kiranmai,Li Anping,Kossenkov Andrew V.,et al.The mRNA-edited form of GABRA3 suppresses GABRA3-mediated Akt activation and breast cancer metastasis[J].NATURE COMMUNICATIONS.2016,7:doi:10.1038/ncomms10715.
APA:
Gumireddy, Kiranmai,Li, Anping,Kossenkov, Andrew V.,Sakurai, Masayuki,Yan, Jinchun...&Huang, Qihong.(2016).The mRNA-edited form of GABRA3 suppresses GABRA3-mediated Akt activation and breast cancer metastasis.NATURE COMMUNICATIONS,7,
MLA:
Gumireddy, Kiranmai,et al."The mRNA-edited form of GABRA3 suppresses GABRA3-mediated Akt activation and breast cancer metastasis".NATURE COMMUNICATIONS 7.(2016)