The Role of Crk Adaptor Proteins in Breast Tumorigenesis and Bone Metastasis

We have established a relationship between Crk protein expression and cell proliferation in basal breast cancer. Stable knockdown of Crk protein expression using shRNA in multiple basal breast cancer cell lines decreased both adhesion-independent growth in vitro and proliferation in vivo. Immunohistochemistry to CrkIII, CrkL, and the proliferative marker Ki67 revealed a positive correlation between Crk protein levels and the proliferative index of human basal tumors in a tissue microarray. The association of a Crk gene expression signature with basal tumors and poor prognosis further supports a role for Crk-dependent signaling in the growth of basal tumors. These findings support a requirement for Crk protein expression in basal tumor progression, and identify Crk proteins as an attractive subject for further study and therapeutic intervention in basal tumors.