Function of Akt/PKB signaling to cell motility, invasion and the tumor stroma in cancer

The serine/threonine protein kinase Akt is a major signal transducer of the phosphoinositide 3-kinase (PI 3-K) pathway in all cells and tissues and plays a pivotal role in the maintenance of cellular processes including cell growth, proliferation, survival and metabolism. The frequent aberrant activ...

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Bibliographic Details
Published in:Cellular signalling 2009-04, Vol.21 (4), p.470-476
Main Authors: Chin, Y. Rebecca, Toker, Alex
Format: Article
Language:English
Subjects:
Akt
Animals
Breast cancer
Breast Neoplasms - enzymology
Breast Neoplasms - pathology
Cell Compartmentation
Cell Line, Tumor
Cell motility
Cell Movement - physiology
Cells, Cultured
Female
Fibroblasts - cytology
Fibroblasts - enzymology
Fibrosarcoma - enzymology
Fibrosarcoma - pathology
Humans
Metastasis
Mice
Neoplasm Invasiveness - physiopathology
Neoplasm Metastasis - physiopathology
Neoplasm Proteins - physiology
Neovascularization, Pathologic - enzymology
PI 3-K
Proto-Oncogene Proteins c-akt - antagonists & inhibitors
Proto-Oncogene Proteins c-akt - genetics
Proto-Oncogene Proteins c-akt - physiology
Signal transduction
Signal Transduction - physiology
Stromal Cells - physiology
Vascular Endothelial Growth Factor A - physiology
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Summary:The serine/threonine protein kinase Akt is a major signal transducer of the phosphoinositide 3-kinase (PI 3-K) pathway in all cells and tissues and plays a pivotal role in the maintenance of cellular processes including cell growth, proliferation, survival and metabolism. The frequent aberrant activation of the PI 3-K/Akt pathway in human cancer has made it an attractive therapeutic target. Numerous studies have provided a comprehensive understanding of the specific functions of Akt signaling in cancer cells as well as the surrounding tumor microenvironment and this has informed and enabled the development of therapeutic drugs to target both PI 3-K and Akt. However, recent studies have provided evidence for distinct functions of the three mammalian Akt isoforms, particularly with respect to the regulation of cell motility and metastasis of breast cancer. Here we discuss the mechanisms by which Akt signaling contributes to invasive migration and tumor metastasis, and highlight recent advances in our understanding of the contribution of the Akt pathway in the tumor-associated stroma.
ISSN:0898-6568
1873-3913
DOI:10.1016/j.cellsig.2008.11.015