Regulation of Matrix Metalloproteinases and Invasion by G(alpha 12/13) Proteins in NIH3T3 Mouse Fibroblast Cells

The G12 subfamily of the heterotrimeric G proteins, G(alpha 12) and G(alpha 13), has been implicated as an important signaling component in various cellular processes including oncogenesis and cells invasion. Our previous report showed that the expression of an activated mutant of G(alpha 12) (G(alpha 12)QL) or G(alpha 13) (G(alpha 13)QL) leads to cell invasion in MCF10A human breast epithelial cells. The present study aimed to investigate the role of G(alpha 12) and G(alpha 13) in the malignant phenotypic conversion of NIH3T3 mouse fibroblast cells. G(alpha 12)QL and G(alpha 13)QL induced an invasive phenotype in NIH3T3 cells. In addition, the activation of G(alpha 12) and G(alpha 13) upregulated matrix metalloproteinase (MMP)-2 while MMP-9 was not affected by either G(alpha 12)QL or G(alpha 13)QL. Using female NOD/SCID mice injected with NIH3T3 cells stably expressing G(alpha 12)QL, we provided in vivo confirmation of G(alpha 12)-mediated MMP-2 upregulation. Taken together, this study elucidated the role of G(alpha 12/13) in regulating malignant phenotypic conversion of NIH3T3 fibroblast cells, validating the role of G(alpha 12/13) in tumorigenesis.