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Gut. 2014 Nov;63(11):1821-9. doi: 10.1136/gutjnl-2013-306704. Epub 2014 Aug 27.

Dependence receptors and colorectal cancer.

Author information

1
Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', LabEx DEVweCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, Lyon, France.

Abstract

The research on colorectal cancer (CRC) biology has been leading the oncology field since the early 1990s. The search for genetic alterations has allowed the identification of the main tumour suppressors or oncogenes. Recent work obtained in CRC has unexpectedly proposed the existence of novel category of tumour suppressors, the so-called 'dependence receptors'. These transmembrane receptors behave as Dr Jekyll and Mr Hyde with two opposite sides: they induce a positive signalling (survival, proliferation, differentiation) in presence of their ligand, but are not inactive in the absence of their ligand and rather trigger apoptosis when unbound. This trait confers them a conditional tumour suppressor activity: they eliminate cells that grow abnormally in an environment offering a limited quantity of ligand. This review will describe how receptors such as deleted in colorectal carcinoma (DCC), uncoordinated 5 (UNC5), rearranged during transfection (RET) or TrkC constrain CRC progression and how this dependence receptor paradigm may open up therapeutical perspectives.

KEYWORDS:

CELL DEATH; COLORECTAL CANCER; ONCOGENES

PMID:
25163468
DOI:
10.1136/gutjnl-2013-306704
[Indexed for MEDLINE]

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