Netrin-1 and its receptors in tumorigenesis.
Netrin-1 and its receptors DCC (deleted in colorectal cancer) and the UNC5 orthologues (human UNC5A-D and rodent UNC5H1-4) define a new mechanism for both the positive (induction) and negative (suppression) regulation of apoptosis. Accumulating evidence implies that for human cancers, this positive signalling pathway is frequently inactivated. Surprisingly, binding of netrin-1 to its receptors inhibits tumour suppressor p53-dependent apoptosis, and p53 is directly involved in transcriptional regulation of netrin-1 and its receptors. So, the netrin-1 receptor pathways probably play an important part in tumorigenesis.
Arakawa
Hirofumi
H
Cancer Medicine and Biophysics Division, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. harakawa@gan2.res.ncc.go.jp
D001369:Axons / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D000075389:DCC Receptor; D016163:Genes, DCC; D006801:Humans; D019656:Loss of Heterozygosity; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D009414:Nerve Growth Factors / Q000235:genetics*; D000075386:Netrin Receptors; D000075388:Netrin-1; D011956:Receptors, Cell Surface / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501909:DCC protein, human; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C115727:UNC5C protein, human; D000075388:Netrin-1