PTEN in brain tumors

Abstract

The tumor suppressor PTEN dephosphorylates phospholipids generated through the activity of PI3K. PTEN thus antagonizes PI3K activity and regulates a multitude of cellular processes such as angiogenesis, motility, invasiveness, survival and proliferation, all of which can initiate and sustain the malignant phenotype. Although PTEN’s lipid phosphatase activity is key to its tumor suppressive functions, it also dephosphorylates protein substrates and interacts with other key regulatory molecules, salient among them the tumor suppressor p53. Given the critical roles of PTEN in cellular homeostasis, it is not surprising that both PTEN expression levels and PTEN protein activities are tightly controlled by a complex conglomeration of molecules that regulate post-translational modifications, subcellular localization, transcriptional activation and transcriptional repression. As one of the most commonly altered molecules in human disease, PTEN plays an important role in a myriad of signaling cascades, and plays a central role in normal brain development and brain tumor pathogenesis. As such it influences prognosis of human cancer, predicts response to therapy, constitutes the lynchpin of genetic syndromes, and may underlie neurocognitive abnormalities such as autism spectrum disorders and Alzheimer’s disease. Thus, targeting PTEN and its signaling affiliates sows the seeds for combating not only cancer but also neurocognitive disorders.

Keywords::

• autism
• glioblastoma
• molecularly targeted therapy
• p53
• phosphatase
• phosphoinositide 3-kinase
• phosphorylation
• PI3K
• PTEN
• tumor suppressor

Acknowledgement

We would like to thank Tanja Tamguney for contributing to Figure 2.

Financial & competing interests disclosure

Work in the authors’ laboratories is supported in part by the NIH Brain Tumor SPORE grant P50 CA097257, The Nancy and Stephen Grand Philanthropic Fund and the Thrasher Research Fund. David Stokoe is currently an employee of Genentech, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this review manuscript.