Expression levels of the focal adhesion-associated proteins paxillin and p130^CAS in canine and feline mammary tumors

Abstract

-Paxillin and p130 CAS are two adaptor proteins localized at the focal adhesions which play an important role in cell signaling, cell motility and oncogenic transformation. In this study we evaluated the levels of paxillin and p130 CAS in feline and canine mammary tumor tissues at different stages of malignancy. The results obtained by Western blotting analysis showed no significant differences in the amounts of paxillin and p130 CAS between normal and non-invasive tumor tissues. By contrast, mammary tumor tissues with the invasive phenotype showed lower levels of paxillin P < 0.01 and higher levels of p130 CAS P < 0.001 than normal tissues. The decrease P < 0.001 of the amount of paxillin and the increase P < 0.001 of p130 CAS levels were correlated with the progression stage of malignancy. Since paxillin and p130 CAS are involved in regulating cell migration, our results suggest that low levels of paxillin together with high levels of p130 CAS expression may cause certain breast cancers to be more motile and possibly more aggressive. Thus, both paxillin and p130 CAS may represent useful prognosticators of feline and canine breast cancer malignancy.paxillin / p130 CAS / mammary tumor / cat / dog

Paxillin: Adapting to Change

“…Paxillin tyrosine phosphorylation changes were not observed in conjunction with increases in paxillin levels (287) consistent with increased invasiveness being associated with the formation of a novel signaling invadopodia complex that includes paxillin, cortactin, and PKC but not FAK (21). However, a decrease in paxillin levels and an increase in p130cas levels have been associated with metastatic breast cancers in canine and feline models (237). This is consistent with the demonstration of a functional antagonism between paxillin and p130cas with respect to epithelial-mesenchymal transition and motility in a murine mammary cell model (316).…”

Insulin-like growth factor-I signaling in human neuroblastoma cells

“…In contrast, paxillin expression is significantly decreased in N cells compared to S cells, suggesting that paxillin expression may be important in determining tumor phenotype. Reports from other cancer cell lines show that invasive nonadherent tumors express reduced levels of paxillin (Scibelli et al, 2003), while overexpression of paxillin results in decreased motility and tumorigenesis .…”

Crk-Associated Substrate Tyrosine Phosphorylation Sites Are Critical for Invasion and Metastasis of Src-Transformed Cells

“…In breast cancer patients, high CAS/BCAR1 levels are associated with early disease recurrence, poor response to tamoxifen treatment, and lower overall survival (28,29). Increased CAS levels also correlate with an invasive phenotype in feline and canine mammary tumors (30). Further supporting a possible role for CAS in cancer progression to malignancy, we recently reported that CAS reexpression in CASÀ/À mouse embryo fibroblasts transformed by oncogenic Src resulted in a striking enhancement of Matrigel invasiveness associated with increased activation of matrix metalloproteinase-2 (MMP-2) and formation of large podosomal structures containing tyrosine-phosphorylated CAS (31).…”