Year: 2009
Type: article
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.
Source: Cancer Research
Language: English
Subfield: Immunology and Allergy
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1062996462, G156276794, The role of HEF1/NEDD9 protein in proliferation and invasion of metastatic breast cancer, G2017280508, G2445645941, G2648806149, G3371651731, G3771026464, The Role of HEF1 in Ovarian Cancer Development, Progression, and Metastasis, Cas Protein Regulation of EMT in Cancer, G47070370, G521800421, G5850682332, G6408618350, G6455403188, LY-1 B Cells: Developmental Origins and V Gene Biases, G9000027172, G921727105
OpenAlex ID: W2103547450