The ubiquitin E3 ligase WWP1 decreases CXCL12-mediated MDA231 breast cancer cell migration and bone metastasis
文献类型：期刊论文
| 作者 | Subik K1; Shu L1; Wu CY1; Liang QQ1; Hicks D1; Boyce B1; Schiffhauer L1; Chen D2; Chen CS3; Tang P1 |
| 刊名 | BONE
 |
| 出版日期 | 2012 |
| 卷号 | 50期号:4页码:813-823 |
| 关键词 | WWP1 Breast cancer Bone metastasis CXCR4 Degradation |
| 通讯作者 | lianping_xing@urmc.rochester.edu |
| 合作状况 | 其它 |
| 英文摘要 | 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. |
| 收录类别 | SCI |
| 资助信息 | 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). |
| 语种 | 英语 |
| WOS记录号 | WOS:000301967400001 |
| 公开日期 | 2012-09-13 |
| 源URL | [http://159.226.149.42:8088/handle/152453/7083]  |
| 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.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.,...&Xing LP[*].(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. |
入库方式： OAI收割
来源：昆明动物研究所
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