PI3K/AKT Pathway and the Epithelial-Mesenchymal Transition

Chapter
Part of the Cancer Genetics book series (CANGENETICS)

Abstract

The catalytic subunit of the phosphatidylinositol 3-kinase (PIK3; EC 2.7.1.137) is one of the most frequently mutated gene in human cancers, as is its inhibitor PTEN. By some estimates, PIK3CA carries gain-of-function mutations in 32% of colorectal cancers, 36% of hepatocellular carcinomas, 36% of endometrial carcinomas, 25% of breast carcinomas, 15% of anaplastic oligodendrogliomas, and 5% of medulloblastomas and anaplastic astrocytomas (recently reviewed in Velculescu, 2008). Similarly, spontaneous mutations in PTEN are found in 50% of endometrial cancers, 30% of glioblastomas, 10% of prostate, and 5% of breast carcinomas. Moreover, inherited mutations in PTEN lead to a variety of conditions, such as Cowden syndrome, which are associated with an increased risk of cancer (recently reviewed in Keniry and Parsons, 2008). In addition, frequent alterations and hyperactivation of AKT kinases have been described in almost every tumor type studied (reviewed in Bellacosa et al., 2005; Brugge et al., 2007). While many of the downstream effectors of the AKT pathway are involved in cell autonomous processes (i.e., cell cycle and apoptosis), the following chapter will focus on the implications of aberrant AKT signaling for epithelial–mesenchymal transition, in particular on the PI3K–AKT–NF-κB–Snail pathways in EMT with emphasis on E-cadherin regulation.

Notes

Acknowledgments

We would like to thank the staff at the Bellacosa and Larue laboratories for constructive discussions and rigorous dedication to this field of research. We apologize to colleagues whose work is not cited – despite its value – due to space constraints. This work was supported by NIH grants CA78412, CA105008, and CA06927. Additional support was provided by an appropriation from the Commonwealth of Pennsylvania to the Fox Chase Cancer Center. The Ligue Contre le Cancer – comité de l’Oise, INCa, cancéropole IdF and Institut Curie also provided support.

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Human Genetics ProgramEpigenetics and Progenitor Cells Program, Fox Chase Cancer CenterPhiladelphiaUSA
  2. 2.Laboratory of Developmental TherapeuticsRegina Elena Cancer CenterRomeItaly
  3. 3.Lionel LarueUMR 146 CNRS - Institut CurieOrsayFrance

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