Silencing of CXCR4 blocks breast cancer metastasis

• Type of Material: Article
• Authors: Zhongxing Liang, Emory University; Younghyoun Yoon, Emory University; John Votaw, Emory University; Mark Goodman, Emory University; Larry Williams, Emory University; Hyunsuk Shim, Emory University
• Language: English
• Date: 2005-02-01
• Publisher: American Association for Cancer Research
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: ©2005 American Association for Cancer Research.
• Title of Journal or Parent Work: Cancer Research
• ISSN: 0008-5472
• Volume: 65
• Issue: 3
• Start Page: 967
• End Page: 971
• Grant/Funding Information: Grant support: Georgia Cancer Coalition Distinguished Cancer Scientist Development Fund (H. Shim) and the AACR-Cancer Research and Prevention Foundation Fellowship in Cancer Prevention Research (Z. Liang).
• Keywords: DELIVERY; Life Sciences & Biomedicine; Oncology; SIRNAS; EXPRESSION; INHIBITION; POTENT; SUPPRESSION; Science & Technology; SMALL INTERFERING RNAS; MAMMALIAN-CELLS; MICE
• Research Categories: Health Sciences, Oncology; Biology, Cell

Abstract

RNA interference technology, silencing targeted genes in mammalian cells, has become a powerful tool for studying gene function. For the first time in cancer research, we show that direct injection of a pool of naked small interfering RNA (siRNA) duplexes can prevent tumorigenesis in an animal model, suggesting a novel preventive and therapeutic strategy for cancer management. As a model system, we used siRNA duplexes of CXCR4 to block breast cancer metastasis. Here, we show that blocking CXCR4 expression at the mRNA level by a combination of two siRNAs impairs invasion of breast cancer cells in Matrigel invasion assay and inhibits breast cancer metastasis in an animal model. Targeting more than one site of the target gene may be important to overcome the functional redundancy of other variants of a single gene, especially in in vivo experiments. Moreover, our studies confirm the necessity of CXCR4 in breast cancer metastasis.