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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.
Bergan, "MAPKAPK2 and HSP27 are downstream effectors of p38 MAP kinase-mediated matrix metalloproteinase type 2 activation and cell invasion in human prostate cancer," Oncogene, vol.
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- MAPK/ERK kinase kinase 1
- MAPK/ERK kinase kinase 15
- MAPK/ERK kinase kinase 2
- MAPK/ERK kinase kinase 3
- MAPK/ERK kinase kinase 4
- MAPK/ERK kinase kinase 5
- MAPK/MAK/MRK overlapping kinase
- MAPKK 1
- MAPKK 2
- MAPKK 3
- MAPKK 4
- MAPKK 5
- MAPKK 6
- MAPKK 7
- MAPKSP1 adaptor protein