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 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.
Chin
Y Rebecca
YR
Department of Pathology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, EC/CLS-528, Boston, MA 02215, USA. rchin1@bidmc.harvard.edu
Toker
Alex
A
D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002451:Cell Compartmentation; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D005354:Fibrosarcoma / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000201:enzymology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D017154:Stromal Cells / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D009363:Neoplasm Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C494918:AKT1 protein, human; C494921:AKT2 protein, human; C491754:AKT3 protein, human; C514862:Akt1 protein, mouse; C494922:Akt2 protein, mouse; D051057:Proto-Oncogene Proteins c-akt