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-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

No abstract

Disintegrins, low molecular weight RGD-containing polypeptides isolated from snake venoms, have seen use as integrin antagonists in the field of tumor biology and angiogenesis. In this study, we investigated the molecular mechanism by which the disintegrin echistatin affects cell adhesion and signaling resulting in an apoptotic response in the GD25 cell system. Wild-type GD25 cells, which lack expression of the beta(1) family of integrin, and stable transfectants expressing the A isoform of beta(1) integrin subunit were used. Nanomolar concentrations of echistatin detached fibronectin- and vitronectin-adherent GD25 cells from immobilized substratum. However, prior to inducing detachment of adherent cells, echistatin caused apoptosis as measured by caspase-3 activation. Either cell detachment or apoptotic response induced by echistatin were more pronounced on fibronectin-adherent GD25 cells than on vitronectin-adherent ones. GD25 cell exposure to echistatin caused a reduction of tyrosine phosphorylation levels of pp125(FAK), whereas it didn't affect either Shc tyrosine phosphorylation levels or Shc-Grb2 functional association. The down-regulation of pp125(FAK) preceded apoptosis and cell detachment induced by echistatin. Our results indicate that pp125(FAK) and not Shc pathway is involved in echistatin-induced apoptotic response in the GD25 cell system.

In this study, three structurally distinct disintegrins (flavoridin, echistatin, kistrin) were used as molecular probes to further characterize the molecular mechanisms underlying Yersinia enterocolitica infection of host cells. The activity of the three disintegrins on Y. enterocolitica uptake into fibronectin-adherent HeLa cells was evaluated at disintegrin doses which were non-cytotoxic and unable to induce cell detachment. Flavoridin resulted to be the most effective in inhibiting bacterial entry into host cells; echistatin was almost 50% less effective than flavoridin, whereas kistrin was definitely inactive. Our results suggest that alpha(5)beta(1) integrin receptor, which binds flavoridin with higher affinity than the other two disintegrins, plays a major role in Y. enterocolitica uptake into HeLa cells. Furthermore, flavoridin binding to this integrin prevented the disruption of the functional complex FAK-Cas, which occurs in the Y. enterocolitica uptake process.