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

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单位: [1]Wistar Inst Anat & Biol, Dept Tumor Microenvironm & Metastasis, 3601 Spruce St, Philadelphia, PA 19104 USA [2]Univ Washington, Med Ctr, 1959 NE Pacific St, Seattle, WA 98195 USA [3]Fudan Univ, Canc Hosp, Dept Radiat Oncol, 270 Dong An Rd, Shanghai 200032, Peoples R China [4]Dalian Med Univ, Inst Canc Stem Cell, Dept Anat, Coll Basic Med Sci, 9 West Sect Lvshun South Rd, Dalian 116044, Peoples R China [5]Huazhong Univ Sci & Technol,Tongji Hosp,Dept Urol,Tongji Med Coll,Wuhan 430030,Peoples R China [6]Shanghai Jiao Tong Univ, Renji Hosp, Dept Biliary Pancreat Surg, Sch Med, Shanghai 200127, Peoples R China [7]Hosp Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA [8]Univ Penn, Dept Obstet & Gynecol, Perelman Sch Med, Philadelphia, PA 19104 USA
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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.

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大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
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大类 | 1 区 综合性期刊
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Q1 MULTIDISCIPLINARY SCIENCES
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Q1 MULTIDISCIPLINARY SCIENCES

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第一作者单位: [1]Wistar Inst Anat & Biol, Dept Tumor Microenvironm & Metastasis, 3601 Spruce St, Philadelphia, PA 19104 USA
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