| First Author | Izumchenko E | Year | 2009 |
| Journal | Cancer Res | Volume | 69 |
| Issue | 18 | Pages | 7198-206 |
| PubMed ID | 19738060 | Mgi Jnum | J:152685 |
| Mgi Id | MGI:4359528 | Doi | 10.1158/0008-5472.CAN-09-0795 |
| Citation | Izumchenko E, et al. (2009) NEDD9 promotes oncogenic signaling in mammary tumor development. Cancer Res 69(18):7198-206 |
| abstractText | In the past 3 years, altered expression of the HEF1/CAS-L/NEDD9 scaffolding protein has emerged as contributing to cancer metastasis in multiple cancer types. However, whereas some studies have identified elevated NEDD9 expression as prometastatic, other work has suggested a negative role in tumor progression. We here show that the Nedd9-null genetic background significantly limits mammary tumor initiation in the MMTV-polyoma virus middle T genetic model. Action of NEDD9 is tumor cell intrinsic, with immune cell infiltration, stroma, and angiogenesis unaffected. The majority of the late-appearing mammary tumors of MMTV-polyoma virus middle T;Nedd9(-/-) mice are characterized by depressed activation of proteins including AKT, Src, FAK, and extracellular signal-regulated kinase, emphasizing an important role of NEDD9 as a scaffolding protein for these prooncogenic proteins. Analysis of cells derived from primary Nedd9(+/+) and Nedd9(-/-) tumors showed persistently reduced FAK activation, attachment, and migration, consistent with a role for NEDD9 activation of FAK in promoting tumor aggressiveness. This study provides the first in vivo evidence of a role for NEDD9 in breast cancer progression and suggests that NEDD9 expression may provide a biomarker for tumor aggressiveness. |
