Epigenetic control of cancer by neuropeptides.

Neuropeptides act as neurohormones, neurotransmitters and/or neuromodulators. Neuropeptides maintain physiological homeostasis and are paramount in molecular mechanisms of disease progression and regulation, including in cancer. Neuropeptides, by their definition, originate and are secreted from the neuronal cells, they are able to signal to neighboring cells or are released into the blood flow, if they act as neurohormones. The majority of neuropeptides exert their functions through G protein-coupled receptors, with certain exceptions. Although previous studies indicate that neuropeptides function in supporting proliferation of malignant cells in many types of solid tumor, the antitumorigenic action of the neuropeptides and their receptors, for example, in gastric cancers and chondrosarcoma, were also reported. It is known that epigenetically modified chromatin regulates molecular mechanisms involved in gene expression and malignant progression. The epigenetic modifications are genetically heritable, although they do not cause changes in DNA sequence. DNA methylation, histone modifications and miRNA expression are subject to those modifications. While there is substantial data on epigenetic regulation of neuropeptides, the epigenetic control of cancer by neuropeptides is considered to be uncharted territory. The aim of the current review is to describe the involvement of neuropeptides in the epigenetic machinery of cancer based on data obtained from our laboratory and from other authors.