Wednesday, August 29, 2012

Roles of the Akt substrate Girdin in cancer progression, angiogenesis and neurogenesis.

We need angiogenesis and neurogenesis and Akt to help cell migration.  Have Akt lasso those newborn neurons and drag them to the correct spot.
http://w3serv.nagoya-u.ac.jp/coemed/en/meetings/meetings/international/dr-masahide-takahashi-1/
The serine/threonine kinase Akt is involved in a variety of cellular processes including cell proliferation, survival and gene expression. Akt has also been shown to be required for cell migration in different organisms. However, the mechanism by which Akt functions to promote cell migration is not fully understood. We identified a new Akt substrate, Girdin (girders of actin filament) which is an actin-binding protein, and found that Girdin is essential for the integrity of the actin cytoskeleton and cell migration. Girdin is expressed in immature endothelial cells, neuronal cells and some types of cancer cells, such as breast cancer and glioblastoma. Akt phosphorylates serine at position 1416 in Girdin, and phosphorylated Girdin accumulates at the leading edge of migrating cells. Cells expressing mutant Girdin, in which serine 1416 was replaced with alanine, exhibited limited migration and lamellipodia formation. Girdin-deficient mice exhibited neuronal migration defect which results in hypoplasia of the olfactory bulb and granule cell dispersion in the dentate gyrus. In addition, we obtained evidence that Akt-mediated phosphorylation of Girdin promotes VEGF-dependent migration and capillary formation of endothelial cells. Depletion of Girdin also resulted in severe impairment of cancer cell migration and invasion. A significant observation is that Girdin is dispensable for cell migratory events during embryonic development. Our findings suggest that Girdin and its interacting proteins are potential pharmaceutical targets for cancer therapies and pathological angiogenesis, including tumor angiogenesis.

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