The ubiquitin E3 ligase WWP1 decreases CXCL12-mediated MDA231 breast cancer cell migration and bone metastasis

KIZ OpenIR > 科研部门 > 肿瘤生物学（陈策实）

	The ubiquitin E3 ligase WWP1 decreases CXCL12-mediated MDA231 breast cancer cell migration and bone metastasis
	Subik K 1; Shu L 1; Wu CY 1; Liang QQ 1; Hicks D 1; Boyce B 1; Schiffhauer L 1; Chen D 2; Chen CS 3; Tang P 1; Xing LP*1; lianping_xing@urmc.rochester.edu
	2012
发表期刊	BONE
卷号	50 期号:4 页码:813-823
合作性质	其它
摘要	Advanced breast cancers preferentially metastasize to bone where cells in the bone microenvironment produce factors that enhance breast cancer cell homing and growth. Expression of the ubiquitin E3 ligase WWP1 is increased in some breast cancers, but its role in bone metastasis has not been investigated. Here, we studied the effects of WWP1 and itch, its closest family member, on breast cancer bone metastasis. First, we immunostained a multi-tumor tissue microarray and a breast cancer tissue microarray and demonstrated that WWP1 and ITCH are expressed in some of breast cancer cases. We then knocked down WWP1 or itch in MDA-MB-231 breast cancer cells using shRNA and inoculated these cells and control cells into the left ventricle of athymic nude mice. Radiographs showed that mice given shWWP1 cells had more osteolytic lesions than mice given control MDA-MB-231 cells. Histologic analysis confirmed osteolysis and showed significantly increased tumor area in bone marrow of the mice. WWP1 knockdown did not affect cell growth, survival or osteoclastogenic potential, but markedly increased cell migration toward a CXCL12 gradient in vitro. Furthermore, WWP1 knockdown significantly reduced CXCL12-induced CXCR4 lysosomal trafficking and degradation. In contrast, itch knockdown had no effect on MDA-MB-231 cell bone metastasis. Taken together, these findings demonstrate that WWP1 negatively regulates cell migration to CXCL12 by limiting CXCR4 degradation to promote breast cancer metastasis to bone and highlight the potential utility of WWP1 as a prognostic indicator for breast cancer bone metastasis. (C) 2012 Elsevier Inc. All rights reserved.
关键词	Wwp1 Breast Cancer Bone Metastasis Cxcr4 Degradation
资助者	This work wassupportedby researchgrants fromtheNational Insti- tutes of Health PHS awards (AR48697 to LX, AR43510 to BFB). Kristina Subik was supported by a research fellowship from the Department of Pathology and Laboratory Medicine, University of Rochester Medical Center. Portion of statistical analysis was supported by the CTSI grant (UL1 RR024160-01 to University of Rochester Medical Center). ; This work wassupportedby researchgrants fromtheNational Insti- tutes of Health PHS awards (AR48697 to LX, AR43510 to BFB). Kristina Subik was supported by a research fellowship from the Department of Pathology and Laboratory Medicine, University of Rochester Medical Center. Portion of statistical analysis was supported by the CTSI grant (UL1 RR024160-01 to University of Rochester Medical Center). ; This work wassupportedby researchgrants fromtheNational Insti- tutes of Health PHS awards (AR48697 to LX, AR43510 to BFB). Kristina Subik was supported by a research fellowship from the Department of Pathology and Laboratory Medicine, University of Rochester Medical Center. Portion of statistical analysis was supported by the CTSI grant (UL1 RR024160-01 to University of Rochester Medical Center). ; This work wassupportedby researchgrants fromtheNational Insti- tutes of Health PHS awards (AR48697 to LX, AR43510 to BFB). Kristina Subik was supported by a research fellowship from the Department of Pathology and Laboratory Medicine, University of Rochester Medical Center. Portion of statistical analysis was supported by the CTSI grant (UL1 RR024160-01 to University of Rochester Medical Center).
收录类别	SCI
语种	英语
资助者	This work wassupportedby researchgrants fromtheNational Insti- tutes of Health PHS awards (AR48697 to LX, AR43510 to BFB). Kristina Subik was supported by a research fellowship from the Department of Pathology and Laboratory Medicine, University of Rochester Medical Center. Portion of statistical analysis was supported by the CTSI grant (UL1 RR024160-01 to University of Rochester Medical Center). ; This work wassupportedby researchgrants fromtheNational Insti- tutes of Health PHS awards (AR48697 to LX, AR43510 to BFB). Kristina Subik was supported by a research fellowship from the Department of Pathology and Laboratory Medicine, University of Rochester Medical Center. Portion of statistical analysis was supported by the CTSI grant (UL1 RR024160-01 to University of Rochester Medical Center). ; This work wassupportedby researchgrants fromtheNational Insti- tutes of Health PHS awards (AR48697 to LX, AR43510 to BFB). Kristina Subik was supported by a research fellowship from the Department of Pathology and Laboratory Medicine, University of Rochester Medical Center. Portion of statistical analysis was supported by the CTSI grant (UL1 RR024160-01 to University of Rochester Medical Center). ; This work wassupportedby researchgrants fromtheNational Insti- tutes of Health PHS awards (AR48697 to LX, AR43510 to BFB). Kristina Subik was supported by a research fellowship from the Department of Pathology and Laboratory Medicine, University of Rochester Medical Center. Portion of statistical analysis was supported by the CTSI grant (UL1 RR024160-01 to University of Rochester Medical Center).
WOS记录号	WOS:000301967400001
引用统计	被引频次：22[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/7083
专题	科研部门_肿瘤生物学（陈策实）科研部门_动物模型与人类重大疾病机理重点实验室
通讯作者	lianping_xing@urmc.rochester.edu
作者单位	1.Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA 2.Department of Orthopedics, University of Rochester Medical Center, Rochester, NY 14642, USA 3.Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China
推荐引用方式 GB/T 7714	Subik K,Shu L,Wu CY,et al. The ubiquitin E3 ligase WWP1 decreases CXCL12-mediated MDA231 breast cancer cell migration and bone metastasis[J]. BONE,2012,50(4):813-823.
APA	Subik K.,Shu L.,Wu CY.,Liang QQ.,Hicks D.,...&lianping_xing@urmc.rochester.edu.(2012).The ubiquitin E3 ligase WWP1 decreases CXCL12-mediated MDA231 breast cancer cell migration and bone metastasis.BONE,50(4),813-823.
MLA	Subik K,et al."The ubiquitin E3 ligase WWP1 decreases CXCL12-mediated MDA231 breast cancer cell migration and bone metastasis".BONE 50.4(2012):813-823.

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