Netrin-1 and its receptors in tumorigenesis

H Arakawa - Nature Reviews Cancer, 2004 - nature.com
Nature Reviews Cancer, 2004nature.com
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 …
Abstract
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.
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