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DOI | 10.1038/ncomms15998 |
Interplay between c-Src and the APC/C co-activator Cdh1 regulates mammary tumorigenesis | |
Han, Tao1; Jiang, Shulong1,2,3; Zheng, Hong4; Yin, Qing1; Xie, Mengyu4,5; Little, Margaret R.1,6; Yin, Xiu1,2; Chen, Ming7,8; Song, Su Jung7,9; Beg, Amer A.4,10; Pandolfi, Pier Paolo7; Wan, Lixin1,11 | |
2019-08-16 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2019 |
卷号 | 10 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Peoples R China; South Korea |
英文摘要 | The Anaphase Promoting Complex (APC) coactivator Cdh1 drives proper cell cycle progression and is implicated in the suppression of tumorigenesis. However, it remains elusive how Cdh1 restrains cancer progression and how tumor cells escape the inhibition of Cdh1. Here we report that Cdh1 suppresses the kinase activity of c-Src in an APC-independent manner. Depleting Cdh1 accelerates breast cancer cell proliferation and cooperates with PTEN loss to promote breast tumor progression in mice. Hyperactive c-Src, on the other hand, reciprocally inhibits the ubiquitin E3 ligase activity of APC(Cdh1) through direct phosphorylation of Cdh1 at its N-terminus, which disrupts the interaction between Cdh1 and the APC core complex. Furthermore, pharmacological inhibition of c-Src restores APCCdh1 tumor suppressor function to repress a panel of APCCdh1 oncogenic substrates. Our findings reveal a reciprocal feedback circuit of Cdh1 and c-Src in the crosstalk between the cell cycle machinery and the c-Src signaling pathway. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000481604800001 |
WOS关键词 | ANAPHASE PROMOTING COMPLEX/CYCLOSOME ; TYROSINE KINASE STRUCTURE ; CELL-CYCLE ; BINDING ; FAMILY ; PROTEIN ; ACCUMULATION ; STABILITY ; SUBSTRATE ; COMPLEX |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203373 |
专题 | 资源环境科学 |
作者单位 | 1.H Lee Moffitt Canc Ctr & Res Inst, Dept Mol Oncol, Tampa, FL 33612 USA; 2.Jining Med Univ, Dept Oncol, Affiliated Jining Peoples Hosp 1, Jining 272000, Shandong, Peoples R China; 3.China Acad Chinese Med Sci, Guanganmen Hosp, Dept Oncol, Beijing 100053, Peoples R China; 4.H Lee Moffitt Canc Ctr & Res Inst, Dept Immunol, Tampa, FL 33612 USA; 5.Univ S Florida, Dept Canc Biol PhD Program, Tampa, FL 33620 USA; 6.Nova Southeastern Univ, Ft Lauderdale, FL 33314 USA; 7.Harvard Med Sch, Beth Israel Deaconess Canc Ctr, Beth Israel Deaconess Med Ctr, Canc Res Inst,Dept Med & Pathol, Boston, MA 02215 USA; 8.Duke Univ, Sch Med, Duke Canc Inst, Dept Pathol, Durham, NC 27710 USA; 9.Soonchunhyang Univ, Soonchunhyang Inst Medi Bio Sci, Cheonan Si 31151, Chungcheongnam, South Korea; 10.H Lee Moffitt Canc Ctr & Res Inst, Dept Thorac Oncol, Tampa, FL 33612 USA; 11.H Lee Moffitt Canc Ctr & Res Inst, Dept Cutaneous Oncol, Tampa, FL 33612 USA |
推荐引用方式 GB/T 7714 | Han, Tao,Jiang, Shulong,Zheng, Hong,et al. Interplay between c-Src and the APC/C co-activator Cdh1 regulates mammary tumorigenesis[J]. NATURE COMMUNICATIONS,2019,10. |
APA | Han, Tao.,Jiang, Shulong.,Zheng, Hong.,Yin, Qing.,Xie, Mengyu.,...&Wan, Lixin.(2019).Interplay between c-Src and the APC/C co-activator Cdh1 regulates mammary tumorigenesis.NATURE COMMUNICATIONS,10. |
MLA | Han, Tao,et al."Interplay between c-Src and the APC/C co-activator Cdh1 regulates mammary tumorigenesis".NATURE COMMUNICATIONS 10(2019). |
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