Review
Cell Death and Differentiation (2005) 12, 1044–1056. doi:10.1038/sj.cdd.4401707
The brain within the tumor: new roles for axon guidance molecules in cancers
Edited by P Mehlen
A Chédotal1, G Kerjan1 and C Moreau-Fauvarque1
1CNRS UMR7102, Equipe Développement Neuronal, Université Paris 6, Batiment B, Case 12, 9 Quai Saint-Bernard, 75005 Paris, France
Correspondence: A Chédotal, CNRS UMR7102, Equipe Développement Neuronal, Université Paris 6, Batiment B, Case 12, 9 Quai Saint-Bernard, 75005 Paris, France. Tel: +33-144273414; Fax: +33-144272636; E-mail: chedotal@infobiogen.fr
Received 28 December 2004; Revised 16 May 2005; Accepted 25 May 2005.
Abstract
Slits, semaphorins and netrins are three families of proteins that can attract or repel growing axons and migrating neurons in the developing nervous system of vertebrates and invertebrates. Recent studies have shown that they are widely expressed outside the nervous system and that they may play important roles in cancers. Several of the genes encoding these proteins are localized on chromosomal region associated with frequent loss-of-heterozygosity in tumors and cancer cell lines and there is also significant hypermethylation of their promoter suggesting that they may act as tumor suppressors. In addition, proteins in all these families and their receptors appear to control the vascularization of the tumors. Last, many axon guidance molecules also regulate cell migration and apoptosis in normal and tumorigenic tissues. Overall, this suggests that molecules that could mimick or block the activity of axon guidance molecules may be used as therapeutic agents for the treatment of malignancy.
Keywords:
slit, semaphorin, netrin, plexin, apoptosis, migration, angiogenesis, tumor suppressor
Abbreviations:
Abl, abelson; AHV, alcelaphine herpes virus; ALPS, agrin/laminin/perlecan/slit; CSPG, chondroitin sulfate proteoglycan; DCC, deleted in colorectal cancer; DNA, desoxyribonucleic acid; Dpp, decapentaplegic; Dutt1, deleted in U2020 cells; FNIII, fibronectin type III; GEF, guanine exchange factor; GPI, glycosyl phosphate inositol; GTP, guanine tri-phosphate; HSP, heparan sulfate proteoglycan; HUVEC, human umbilical vein endothelial cell; Ig, immunoglobulin; L(2)gl, lethal giant larvae; LG, laminin G; LOH, loss of heterozygosity; LRR, leucine rich repeat domains; MAPK, microtubule associated protein kinase; MDR, multidrug resistance; mRNA, messenger ribonucleic acid; MRS, Met related sequence; NRP1, neuropilin-1; PAE, porcin aortic endothelial; PDZ, PSD-95/Dlg/Z0-1; PI3K, phosphatidyl inositol 3 kinase; PPARs, peroxisome proliferator activated receptors; RGM, Repulsive Guidance Molecule; RNA, ribonucleic acid; Robo, roundabout; SDF-1, stromal-derived factor-1; Sema, semaphorin; TGF, tumor growth factor; TIM, T-cell, immunoglobulin and mucin domain proteins; VEGF, vascular endothelial growth factor
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