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Semin Cell Dev Biol. 2016 Oct;58:118-26. doi: 10.1016/j.semcdb.2016.06.002. Epub 2016 Jun 3.

Contextual signaling in cancer.

Author information

1
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States.
2
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States. Electronic address: gutmannd@wustl.edu.

Abstract

The formation and maintenance of an organism are highly dependent on the orderly control of cell growth, differentiation, death, and migration. These processes are tightly regulated by signaling cascades in which a limited number of molecules dictate these cellular events. While these signaling pathways are highly conserved across species and cell types, the functional outcomes that result from their engagement are specified by the context in which they are activated. Using the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome as an illustrative platform, we discuss how NF1/RAS signaling can create functional diversity at multiple levels (molecular, cellular, tissue, and genetic/genomic). As such, the ability of related molecules (e.g., K-RAS, H-RAS) to activate distinct effectors, as well as cell type- and tissue-specific differences in molecular composition and effector engagement, generate numerous unique functional effects. These variations, coupled with a multitude of extracellular cues and genomic/genetic changes that each modify the innate signaling properties of the cell, enable precise control of cellular physiology in both health and disease. Understanding these contextual influences is important when trying to dissect the underlying pathogenic mechanisms of cancer relevant to molecularly-targeted therapeutics.

KEYWORDS:

Astrocyte; Glioma; NF1; Nervous system; Neuron; RAS; mTOR

PMID:
27269372
PMCID:
PMC5028257
DOI:
10.1016/j.semcdb.2016.06.002
[Indexed for MEDLINE]
Free PMC Article

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