The PAK-4 project - Inhibitors of PAK-4 for interfering with metastasis of cancer cells
Indication: Cancer
Targeted mechanism: PAK-4-dependent metastasis of cancer cells
Founding researcher: Staffan Strömblad, Karolinska Institutet
Background
PAK-4 belongs to the p21-activated kinase (PAK) family that contains homologous serine/threonine protein kinases acting as downstream effectors of the small GTPases Cdc42 and Rac. So far, six human PAKs (hPAKs) have been identified, classified into two groups: group I including PAK1–3 and group II including PAK4–6. PAK4 is the first identified member of the group II PAKs, and is implicated in cytoskeletal reorganization and filopodia formation. Importantly, PAK4 was recently found to be overexpressed in 78% of a variety of human cancer cell lines, an overexpression that might be mediated by gene amplification and may play a role in Ras-mediated transformation. The group of Staffan Strömblad has recently identified its major role in integrin-dependent breast cancer cell motility.
Current status
The approach is to screen Actar´s compound library of small molecules using a serine/threonine specific kinase assay with purified recombinant PAK-4.
Currently the project has identifies several compounds that are now
tested in cellular assay investigating cell migration and motility.
The goal is the identify compounds that selective inhibit PAK-4 and
ultimately blocks metastasis and to develop these compounds in to new
anticancer drugs.