Signaling through the PI 3-K, Akt, and SGK Pathway in Breast Cancer Progression
Annual summary rept. 20 Sep 2011-29 Sep 2012
BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
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The aggressive behavior of malignant breast cancer is determined by a complex array of signaling pathways that regulate cell growth, survival and migration. The PI 3-K-Akt pathway has been linked to all of these responses. The current paradigm states thasignaling promotes cancer progression. Many of the enzymes that regulate PI 3-K signaling are frequently mutated in human breast cancer, t deregulated PI 3-K-Akt thereby up-regulating Akt activity and increasing tumor cell growth and survival. This is best illustrated by the finding that the catalytic subunit of PI 3-K, PIK3CA, is the most frequently mutated oncogene in breast cancer. However, recent studies have demonstrated that distinct Akt isoforms can either inhibit or enhance breast cancer cell invasive migration and metastasis in vitro and in vivo, probably by phosphorylating a Afadin protein loss of expression is associated with poor outcome in breast cancer patients. The most significant finding of this research thus far is that Afadin isoform 3, which is the longer, ubiquitously expressed form of the protein, is a substrate of Akt, down stream of the PI-3K pathway. This protein translocates to the nucleus following phosphorylation by Akt, which leads to elevated migratory characteristics.
- Medicine and Medical Research