MetaStat reported MENA-induced fibronectin remodeling, tumor cell adhesion and invasion were reversed to MENA-null levels when treated with MAPKAPK2 inhibitors in vitro.
MAPKAPK2 inhibitor monotherapy reduced lung metastasis similar to the previously published effects of MENA deficiency in the MMTV-PyMT murine model.
This result is actually reasonable, because the direct downstream target of p38, MAPKAPK2, was also downregulated, whereas the downstream targets of Erk1/2, MSK1, and p90RSK were unchanged.
Subsequently, MAPKAPK2 phosphorylates CREB (cAMP response element binding protein) and other transcription factors .
"These results confirm our pathway forward for development of MAPKAPK2
inhibitors selected for specificity against the Mena protein." MetaStat has received the final milestone payment of approximately $100,000 and completed its obligations under the pilot research agreement.
and HSP27 are downstream effectors of p38 MAP kinase-mediated matrix metalloproteinase type 2 activation and cell invasion in human prostate cancer," Oncogene, vol.