KMS KUNMING INSTITUTE OF ZOOLOGY.CAS
| Loss of TDP43 inhibits progression of triple-negative breast cancer in coordination with SRSF3 | |
| Hao Ke1,2; Limin Zhao1,2; Honglei Zhang1; Xu Feng1,3; Haibo Xu1,2; Junjun Hao1; Shaowei Wang1,4; Qin Yang1; Li Zou1; Xiaosan Su5; Liqiong Wang6; Chunlian Wu4; Yang Wang7; Jianyun Nie8; Baowei Jiao9 | |
| 2018 | |
| 发表期刊 | pnas
 |
| 卷号 | 115期号:15页码:3426–3435 |
| 摘要 | Aberrant alternative splicing has been highlighted as a potential hallmark of cancer. Here, we identify TDP43 (TAR DNA-binding protein 43) as an important splicing regulator responsible for the unique splicing profile in triple-negative breast cancer (TNBC). Clinical data demonstrate that TDP43 is highly expressed in TNBC with poor prognosis. Knockdown of TDP43 inhibits tumor progression, including proliferation and metastasis, and overexpression of TDP43 promotes proliferation and malignancy of mammary epithelial cells. Deep sequencing analysis and functional experiments indicate that TDP43 alters most splicing events with splicing factor SRSF3 (serine/arginine-rich splicing factor 3), in the regulation of TNBC progression. The TDP43/SRSF3 complex controls specific splicing events, including downstream genes PAR3 and NUMB The effect of reduced metastasis and proliferation upon the knockdown of TDP43 or SRSF3 is mediated by the splicing regulation of PAR3 and NUMB exon 12, respectively. The TDP43/SRSF3 complex and downstream PAR3 isoform are potential therapeutic targets for TNBC. |
| 关键词 | Breast Cance Alternative Splicing Tdp43 Srsf3 Par3 |
| DOI | 10.1073/pnas.1714573115 |
| 语种 | 英语 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.kiz.ac.cn/handle/152453/12266 |
| 专题 | 科研部门_发育的印迹调控与进化学（焦保卫） |
| 作者单位 | 1.State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, 650223 Kunming, China; 2.Kunming College of Life Science, University of Chinese Academy of Sciences, 650223 Kunming, China; 3.Faculty of Life Science and Technology, Kunming University of Science and Technology, 650050 Kunming, China; 4.Key Laboratory of Southwest China Wildlife Resource Conservation (China West Normal University), Ministry of Education, 637009 Nanchong, China; 5.Biomedical Research Center, First Hospital of Kunming, 650011 Kunming, China; 6.Department of Pathology, Yan’an Hospital Affiliated with Kunming Medical University, Kunming, 650051 Yunnan, China; 7.Institute of Cancer Stem Cell, Second Affiliated Hospital Collaborative Innovation Center of Oncology, Dalian Medical University, 116044Dalian, China; 8.Department of Breast Cancer, Third Affiliated Hospital, Kunming Medical University, 650118 Kunming, China; 9.Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, 650223 Kunming, China |
| 推荐引用方式 GB/T 7714 | Hao Ke,Limin Zhao,Honglei Zhang,et al. Loss of TDP43 inhibits progression of triple-negative breast cancer in coordination with SRSF3[J]. pnas,2018,115(15):3426–3435. |
| APA | Hao Ke.,Limin Zhao.,Honglei Zhang.,Xu Feng.,Haibo Xu.,...&Baowei Jiao.(2018).Loss of TDP43 inhibits progression of triple-negative breast cancer in coordination with SRSF3.pnas,115(15),3426–3435. |
| MLA | Hao Ke,et al."Loss of TDP43 inhibits progression of triple-negative breast cancer in coordination with SRSF3".pnas 115.15(2018):3426–3435. |
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| 文件名称/大小 | 文献类型 | 版本类型 | 开放类型 | 使用许可 | ||
| 62.pdf（2152KB） | 期刊论文 | 出版稿 | 开放获取 | CC BY-NC-SA | 请求全文 | |
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