Netrin-1 in the developing enteric nervous system and colorectal cancer

Netrin-1 is a well-characterised chemoattractant involved in neuronal guidance in the developing enteric nervous system (ENS), but it is also a regulator of tumorigenesis. Two of its well-characterised receptors, deleted in colorectal cancer (DCC) and uncoordinated-5 homolog (UNC-5H), belong to a family of dependence receptors that transmit either pro- or anti-apoptosis signals depending on the availability of ligand, in this case netrin-1. This review summarises these two effects of netrin-1 and highlights the additional research needed information about to allow better utilisation of netrin-1 as a therapeutic target for axonal regeneration in the context of colorectal cancer. Netrin-1 is a well-characterised chemoattractant involved in neuronal guidance in the developing enteric nervous system (ENS), but it is also a regulator of tumorigenesis. Two of its well-characterised receptors, deleted in colorectal cancer (DCC) and uncoordinated-5 homolog (UNC-5H), belong to a family of dependence receptors that transmit either pro- or anti-apoptosis signals depending on the availability of ligand, in this case netrin-1. This review summarises these two effects of netrin-1 and highlights the additional research needed information about to allow better utilisation of netrin-1 as a therapeutic target for axonal regeneration in the context of colorectal cancer. these mice have a spontaneous mutation in the tumour suppressor gene Apc and form multiple colorectal adenomas. The APC protein interacts with many other proteins to regulate cell growth and division, and mutations in this gene precede the development of many tumours, particularly in colorectal cancers. small (micron-, or multiples thereof, sized) spherical particles formulated from alginate, a natural polysaccharide, that can be used as a drug delivery system. a cytoplasmic protein that plays a role in regulating apoptosis. a protein that is associated with cell-cycle regulation. a small heme protein found in the inner membrane of mitochondria that can act as a catalyst for oxidation and is involved in apoptosis initiation. a cell line that expresses the EBNA-1 gene from Epstein–Barr virus (EBV), controlled by the highly active cytomegalovirus (CMV) promoter. The EBNA-1 gene is implicated in oncogenesis, latency, and tumour maintenance, although further characterization is needed. the peripheral membrane protein that is localised at the filopodia and lamellipodia tips and regulates cell motility. a major extracellular glycoprotein family of proteins found mainly in the basal lamina. They are important for higher-order structure between cells. the loss of function of one allele of a gene. a biochemical process by which a methyl group is added onto a cytosine or adenine of DNA. This modification can alter gene expression and is associated with cellular differentiation and development. ganglia, or clusters of nerve cell bodies, that are located between the inner and outer muscularis externa layer of the intestines. a transient and multipotent cell population that gives rise to various cell lineages, including peripheral and enteric neurons and glia, melanocytes, craniofacial cartilage and bone, and smooth muscle. located in the inferior ganglion of the vagus nerve – the 10th cranial nerve. These cells project to the medulla and peripheral processes innervating various branches of the vagus nerve. a transcriptional protein that regulates cellular response to stress stimuli. a small signalling G protein family that is involved in intracellular actin dynamics. Members of the family include Cdc42, Rac1, and RhoA. a family Rho GTPase that is involved in regulating cell growth and cytoskeletal reorganisation. a small GTPase protein that regulates the actin-based cytoskeleton. ganglia, or clusters of nerve cell bodies, that are located in the submucosa of the intestines. have a spontaneous mutation in rostral cerebellar malformation that leads to cerebellar and midbrain defects. Although these mice display a functional mutation in UNC-5C, they are viable till adulthood.