Calpain is required for MMP-2 and u-PA expression in SV40 large T-antigen-immortalized cells.

Abstract The absence of both μ- and m-calpain activity, caused by disruption of the capn 4 gene in mice, retarded migration, and disrupted the cytoskeleton, both in primary capn 4 −/− embryonic fibroblasts (mEF) and in capn 4 −/− mEF immortalized with SV40 large T-antigen (TAg). These results are thought to reflect the role of calpain in integrin signaling to the cytoskeleton. The integrins are also involved, together with matrix metalloproteinases (MMP) and plasminogen activators (PA), in cellular invasion. This study therefore aimed to establish whether links exist between the calpain, MMP, and PA systems, using both primary and TAg-immortalized capn 4 +/+ and capn 4 −/− embryonic fibroblasts. Both Matrigel invasion, and expression of MMP-2 and u-PA activities, correlated with calpain expression in TAg-containing cells, but not in primary cells. MMP-2 mRNA synthesis also correlated with calpain expression in the presence of TAg, but u-PA mRNA synthesis was not so correlated. The results suggest that calpain acquires new regulatory roles in the presence of TAg. Calpain is also required for v-Src-mediated transformation. It appears that calpain may have previously unsuspected roles in oncogenic transformation.