Abstract：
: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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Izumchenko E,Singh MK,Plotnikova OV,Tikhmyanova N,Little JL,Serebriiskii IG,Seo S,Kurokawa M,Egleston BL,Klein-Szanto A,Pugacheva EN,Hardy RR,Wolfson M,Connolly DC,Golemis EAdoi
10.1158/0008-5472.CAN-09-0795subject
Has Abstractpub_date
2009-09-15 00:00:00pages
7198-206issue
18eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-09-0795journal_volume
69pub_type
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