Sign up for Table of Contents Alerts.

Email this page

Print this page

Perspectives

Turning the Tables: Myc Activates Wnt in Breast Cancer

Victoria H. Cowling and Michael D. Cole

Purchase article for $19

Subscribe to this journal for $129/year

Previous molecular and genetic data implicate the c-myc gene as a critical downstream effector of the Wnt/TCF pathway in colon cancer. However, the involvement of c-myc in mammary epithelial cell transformation had not been explored. We recently showed that c-Myc induces a profound morphological transformation in human mammary epithelial cells accompanied by anchorage-independent growth. The mechanism of c-Myc transformation was revealed in part through the finding that, in contrast to colon cancer, c-Myc activates the Wnt pathway and endogenous TCF activity by suppressing the Wnt inhibitors DKK1 and SFRP1. Notably, DKK1 and SFRP1 were found to be strongly suppressed in human breast cancer cell lines and their re-expression inhibited the transformed phenotype. We demonstrated that breast cancer cells become dependent on repression of the Wnt inhibitors for cell proliferation, i.e. they have acquired an “oncogene addiction”, suggesting that the Myc-Wnt pathway is an attractive therapeutic target. We propose that a positive feedback loop of c-myc and Wnt signaling operates in breast cancer.

Authors

Victoria H. Cowling

Dartmouth Medical School; Lebanon, NH

Michael D. Cole

Dartmouth Medical School; Lebanon NH, USA

Purchase article for $19

Subscribe to this journal for $129/year