Growth arrest signaling of the Raf/MEK/ERK pathway in cancer

Abstract

The Raf/MEK/extracellular signal-regulated kinase (ERK) pathway has a pivotal role in facilitating cell proliferation, and its deregulated activation is a central signature of many epithelial cancers. However paradoxically, sustained activity of Raf/MEK/ERK can also result in growth arrest in many different cell types. This anti-proliferative Raf/MEK/ERK signaling also has physiological significance, as exemplified by its potential as a tumor suppressive mechanism. Therefore, significant questions include in which cell types and by what mechanisms this pathway can mediate such an opposing context of signaling. Particularly, our understating of the role of ERK1 and ERK2, the focal points of pathway signaling, in growth arrest signaling is still limited. This review discusses these aspects of Raf/MEK/ERK-mediated growth arrest signaling.

Keywords

Raf / MEK1/2 / ERK1/2 / proliferation / growth arrest / non-kinase effect

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Acknowledgements

This work was supported by the National Cancer Institute (R01CA138441) and American Cancer Society (RSGM-10-189-01-TBE). The author wishes to apologize to those whose work is not cited owing to space limitations.

Compliance with ethics guidlines

The author has nothing to declare.

RIGHTS & PERMISSIONS

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg