PTEN regulation of ERK1/2 signaling in cancer

Abstract

Since its discovery, the tumor suppressor phosphatase and tensin homolog (PTEN) has become a molecule with a wide spectrum of functions, which is typically meditated through its lipid phosphatase activity; however, PTEN also functions in a phosphatase-independent manner. It is well established that PTEN regulates several signaling pathways, such as phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), janus kinase (JAK)/signal transducers and activators of transcription (STAT), focal adhesion kinase (FAK), and more recent, extracellular signal-regulated kinase (ERK)1/2, where activation of these pathways typically leads to cancer development and progression. In regard to most of these pathways, the underlining molecular mechanism of PTEN-mediated regulation is well established, but not so much for the ERK1/2 pathway. Indeed, accumulating evidence has shown an inverse correlation between PTEN expression and ERK1/2 in several malignancies. However, the detailed mechanism by which PTEN regulates ERK1/2 is poorly understood. In this review, we discuss the role of PTEN in regulating ERK1/2 by directly targeting shc/Raf/MEK and PI3K/AKT cascades, and a putative cross-talk between the two.

Keywords::

• ERK1/2
• PTEN
• PI3K/AKT
• Raf
• Ras
• cancer

Acknowledgments

Limitations of space preclude extensive citation of literature; we apologize to those whose work is not mentioned herein. Research in this laboratory is supported, in part, by National Institutes of Health grants RCMI22622A (MAC), F31CA153908 (MAC), 2G12RR003062-22 (CVH) and 1P20MD002285 (CVH).

Declaration of interest

The authors report no conflicts of interest.