| First Author | Wheeler DS | Year | 2011 |
| Journal | Oncogene | Volume | 30 |
| Issue | 1 | Pages | 32-42 |
| PubMed ID | 20802536 | Mgi Jnum | J:170222 |
| Mgi Id | MGI:4944157 | Doi | 10.1038/onc.2010.389 |
| Citation | Wheeler DS, et al. (2011) Direct interaction between NHERF1 and Frizzled regulates beta-catenin signaling. Oncogene 30(1):32-42 |
| abstractText | Although Wnt-Frizzled (Fzd) signaling is critical in the pathophysiology of carcinomas, its role in human breast cancer has been difficult to establish. We show here that the adaptor protein Na(+)/H(+) exchange regulatory factor1 (NHERF1), a protein abundantly expressed in normal mammary epithelium, regulates Wnt signaling, maintaining low levels of beta-catenin activation. NHERF1's effects are mediated by direct interactions between one of its PSD-95/drosophila discs large/ZO-1 (PDZ) domains and the C-terminus of a subset of Fzd receptors. Loss of NHERF1 in breast cancer cell lines enhances canonical Wnt signaling and Wnt-dependent cell proliferation. Furthermore, the mammary glands of NHERF1-knockout mice exhibit increased mammary duct density accompanied by increased proliferation and beta-catenin activity. Finally, we demonstrate a negative correlation between NHERF1 expression and nuclear beta-catenin in human breast carcinomas. Taken together, these results provide a novel insight into the regulation of Wnt signaling in normal and neoplastic breast tissues, and identify NHERF1 as an important regulator of the pathogenesis of breast tumors. |
