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Review
. 2013 Mar;30 Suppl(Suppl):S10-8.
doi: 10.1016/j.bbi.2012.11.008. Epub 2012 Dec 1.

Nervous system regulation of the cancer genome

Steven W Cole  1
Affiliations
Review

Nervous system regulation of the cancer genome

Steven W Cole. Brain Behav Immun. 2013 Mar.

Abstract

Genomics-based analyses have provided deep insight into the basic biology of cancer and are now clarifying the molecular pathways by which psychological and social factors can regulate tumor cell gene expression and genome evolution. This review summarizes basic and clinical research on neural and endocrine regulation of the cancer genome and its interactions with the surrounding tumor microenvironment, including the specific types of genes subject to neural and endocrine regulation, the signal transduction pathways that mediate such effects, and therapeutic approaches that might be deployed to mitigate their impact. Beta-adrenergic signaling from the sympathetic nervous system has been found to up-regulated a diverse array of genes that contribute to tumor progression and metastasis, whereas glucocorticoid-regulated genes can inhibit DNA repair and promote cancer cell survival and resistance to chemotherapy. Relationships between socio-environmental risk factors, neural and endocrine signaling to the tumor microenvironment, and transcriptional responses by cancer cells and surrounding stromal cells are providing new mechanistic insights into the social epidemiology of cancer, new therapeutic approaches for protecting the health of cancer patients, and new molecular biomarkers for assessing the impact of behavioral and pharmacologic interventions.

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Figures

FIGURE 1
FIGURE 1
Social signal transduction. Socio-environmental processes regulate human gene expression by activating central nervous system processes that subsequently influence hormone and neurotransmitter activity in the periphery of the body. Peripheral signaling molecules interact with cellular receptors to activate transcription factors, which bind to characteristic DNA motifs in gene promoters to initiate (or repress) gene expression. Only genes that are transcribed into RNA actually impact health and behavioral phenotypes. Individual differences in promoter DNA sequences (e.g., the [G/C] polymorphism shown here) can affect the binding of transcription factors, and thereby influence genomic sensitivity to socio-environmental conditions.
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