This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Luo, M. Articles by Guan, J.-L. Search for Related Content PubMed PubMed Citation Articles by Luo, M. Articles by Guan, J.-L.

Mammary Epithelial-Specific Ablation of the Focal Adhesion Kinase Suppresses Mammary Tumorigenesis by Affecting Mammary Cancer Stem/Progenitor Cells

¹ Divisions of Molecular Medicine and Genetics and ² Hematology and Oncology, Department of Internal Medicine, ³ Comprehensive Cancer Center, and ⁴ Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan

Requests for reprints: Jun-Lin Guan, University of Michigan, 3027 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109. Phone: 734-615-4936; Fax: 734-763-1166; E-mail: jlguan{at}umich.edu.

Key Words: breast cancer • FAK conditional KO mouse • mammary cancer stem cells

Focal adhesion kinase (FAK) has been implicated in the development of cancers, including those of the breast. Nevertheless, the molecular and cellular mechanisms by which FAK promotes mammary tumorigenesis in vivo are not well understood. Here, we show that targeted deletion of FAK in mouse mammary epithelium significantly suppresses mammary tumorigenesis in a well-characterized breast cancer model. Ablation of FAK leads to the depletion of a subset of bipotent cells in the tumor that express both luminal marker keratin 8/18 and basal marker keratin 5. Using mammary stem/progenitor markers, including aldehyde dehydrogenase, CD24, CD29, and CD61, we further revealed that ablation of FAK reduced the pool of cancer stem/progenitor cells in primary tumors of FAK-targeted mice and impaired their self-renewal and migration in vitro. Finally, through transplantation in NOD-SCID mice, we found that cancer stem/progenitor cells isolated from FAK-targeted mice have compromised tumorigenicity and impaired maintenance in vivo. Together, these results show a novel function of FAK in maintaining the mammary cancer stem/progenitor cell population and provide a novel mechanism by which FAK may promote breast cancer development and progression. [Cancer Res 2009;69(2):466–74]