YAP Promotes Breast Cell Proliferation and Survival Partially through Stabilizing the KLF5 Transcription Factor

CORC > 昆明动物研究所 > 昆明动物研究所 > 动物模型与人类重大疾病机理重点实验室 > 肿瘤生物学

	YAP Promotes Breast Cell Proliferation and Survival Partially through Stabilizing the KLF5 Transcription Factor
	Zhi X 1,2; Zhao D 1,2; Zhou ZM 1; Liu R 1; Chen CS[*]1
刊名	AMERICAN JOURNAL OF PATHOLOGY
	2012
卷号	180 期号:6 页码:2452-2461
通讯作者	chenc@mail.kiz.ac.cn
英文摘要	The Yes-associated protein (YAP), an oncoprotein In the Hippo tumor suppressor pathway, regulates tumorigenesis and has been found in a variety of tumors, including breast, ovarian, and hepatocellular cancers. Although YAP functions through its WW domains, the YAP WW domain-binding partners have not yet been completely determined. With this study, we demonstrate that YAP functions partially through its binding to KLF5, a transcription factor that promotes breast cell proliferation and survival. YAP interacted with the KLF5 PY motif through its WW domains, preventing the E3 ubiquitin ligase WWP1 from ubiquitinating KLF5. Overexpression of the wild-type YAP but not the WW domain-mutated YAP up-regulated KLF5 protein levels and mRNA expression levels of KLF5 downstream target genes, including FGFBP1 (alias FGF-BP) and ITGB2. In addition, knockdown of YAP decreased expression levels of KLF5, FGF-BP, and ITGB2. Depletion of either YAP or KLF5 decreased breast cell proliferation and survival in MCF10A and SW527 breast cell lines, and stable knockdown of either YAP or KLF5 suppressed SW527 xenograft growth in mice. The YAP upstream kinase LATS1 suppressed the KLF5-FGF-BP axis, as well as cell growth through YAP signaling. Both YAP and KLF5 are coexpressed in estrogen receptor ER alpha-negative breast cell lines. These findings suggest that KLF5 could be an important transcription factor partner for YAP and may contribute to the Hippo pathway. (AmJ Pathol 2012, 180:2452-2461; http://dx.doi.org/10.1016/j.ajpath.2012.02.025)
收录类别	SCI
资助信息	Supported by a grant from Yunnan Province High-Profile Talents Program (2010CI114) and the National Nature Science Foundation of China Gen- eral Program (81072162, 81120108019, and U1132605).
语种	英语
WOS记录号	WOS:000305101300028
公开日期	2012-09-07
内容类型	期刊论文
源URL	[http://159.226.149.42:8088/handle/152453/7050]
专题	昆明动物研究所_肿瘤生物学昆明动物研究所_动物模型与人类重大疾病机理重点实验室
作者单位	1.Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province,* Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China 2.the Center for Cell Biology and Cancer Research,Albany Medical College, Albany, New York
推荐引用方式 GB/T 7714	Zhi X,Zhao D,Zhou ZM,et al. YAP Promotes Breast Cell Proliferation and Survival Partially through Stabilizing the KLF5 Transcription Factor[J]. AMERICAN JOURNAL OF PATHOLOGY,2012,180(6):2452-2461.
APA	Zhi X,Zhao D,Zhou ZM,Liu R,&Chen CS[*].(2012).YAP Promotes Breast Cell Proliferation and Survival Partially through Stabilizing the KLF5 Transcription Factor.AMERICAN JOURNAL OF PATHOLOGY,180(6),2452-2461.
MLA	Zhi X,et al."YAP Promotes Breast Cell Proliferation and Survival Partially through Stabilizing the KLF5 Transcription Factor".AMERICAN JOURNAL OF PATHOLOGY 180.6(2012):2452-2461.