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DOI | 10.1038/s41467-019-12840-z |
Assembly and activation of the Hippo signalome by FAT1 tumor suppressor | |
Martin, Daniel1; Degese, Maria S.1; Vitale-Cross, Lynn1; Iglesias-Bartolome, Ramiro1,2; Valera, Juan Luis Callejas3,4; Wang, Zhiyong3,4; Feng, Xiaodong3,4; Yeerna, Huwate3; Vadmal, Vachan3; Moroishi, Toshiro4; Thorne, Rick F.5,6; Zaida, Moraima1; Siegele, Bradford7; Cheong, Sok C.8,9; Molinolo, Alfredo A.3; Samuels, Yardena10; Tamayo, Pablo3; Guan, Kun Liang3,4; Lippman, Scott M.3; Lyons, J. Guy11,12,13; Gutkind, J. Silvio1,3,4 | |
2019-10-30 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Australia; Malaysia; Israel |
英文摘要 | Dysregulation of the Hippo signaling pathway and the consequent YAP1 activation is a frequent event in human malignancies, yet the underlying molecular mechanisms are still poorly understood. A pancancer analysis of core Hippo kinases and their candidate regulating molecules revealed few alterations in the canonical Hippo pathway, but very frequent genetic alterations in the FAT family of atypical cadherins. By focusing on head and neck squamous cell carcinoma (HNSCC), which displays frequent FAT1 alterations (29.8%), we provide evidence that FAT1 functional loss results in YAP1 activation. Mechanistically, we found that FAT1 assembles a multimeric Hippo signaling complex (signalome), resulting in activation of core Hippo kinases by TAOKs and consequent YAP1 inactivation. We also show that unrestrained YAP1 acts as an oncogenic driver in HNSCC, and that targeting YAP1 may represent an attractive precision therapeutic option for cancers harboring genomic alterations in the FAT1 tumor suppressor genes. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000437833500001 |
WOS关键词 | PATHWAY ; GROWTH ; YAP ; INDUCTION ; UPSTREAM ; CATENIN ; PROTEIN ; KINASE ; CANCER ; CELLS |
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/204626 |
专题 | 资源环境科学 |
作者单位 | 1.NIH, Oral & Pharyngeal Canc Branch, Bldg 10, Bethesda, MD 20892 USA; 2.NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA; 3.Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA; 4.Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA; 5.Univ Newcastle, Sch Environm & Life Sci, Callaghan, NSW 2308, Australia; 6.Hunter Canc Res Alliance, Callaghan, NSW 2308, Australia; 7.Univ Colorado, Sch Med, Dept Pathol, Aurora, CO 80045 USA; 8.Canc Res, Oral Canc Res Team, Selangor, Malaysia; 9.Univ Malaya, Fac Dent, Dept Oromaxillofacial Surg & Med Sci, Kuala Lumpur, Malaysia; 10.Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel; 11.Univ Sydney, Bosch Inst, Dermatol, Camperdown, NSW 2050, Australia; 12.Royal Prince Alfred Hosp, Canc Serv, Camperdown, NSW 2050, Australia; 13.Centenary Inst, Camperdown, NSW 2050, Australia |
推荐引用方式 GB/T 7714 | Martin, Daniel,Degese, Maria S.,Vitale-Cross, Lynn,et al. Assembly and activation of the Hippo signalome by FAT1 tumor suppressor[J]. NATURE COMMUNICATIONS,2019,9. |
APA | Martin, Daniel.,Degese, Maria S..,Vitale-Cross, Lynn.,Iglesias-Bartolome, Ramiro.,Valera, Juan Luis Callejas.,...&Gutkind, J. Silvio.(2019).Assembly and activation of the Hippo signalome by FAT1 tumor suppressor.NATURE COMMUNICATIONS,9. |
MLA | Martin, Daniel,et al."Assembly and activation of the Hippo signalome by FAT1 tumor suppressor".NATURE COMMUNICATIONS 9(2019). |
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