Journal of Carcinogenesis & Mutagenesis

Abstract

MAGI Scaffolding Molecules Involved in Cancer Cell Signaling

Satoru Matsuda and Yasuko Kitagishi

PTEN is a tumor suppressor gene inactivated in various human cancers, which antagonizes PI3K activity. The PI3K/AKT pathway is frequently activated in cancer, then, the PTEN tumor suppressor may be the major brake of the pathway. Cells that lack functional PTEN gene have constitutively higher levels of PIP3 and activated downstream targets. The PTEN protein binds to the MAGI proteins (MAGIs), which are scaffolding molecules with PDZ domain involved in the regulation of epithelial cell tight-junction assembly. Studies have revealed the potential relevance of the PDZ interactions to cancer cell behaviors. The molecular mechanisms contributing to cancer invasion are the subject of considerable investigation, as a better understanding of the pathogenesis will lead to the development of novel targeted therapies. We review recent studies on the features of PTEN and MAGIs in the signaling pathways involved in cancer progression.