Netrin-1 controls colorectal tumorigenesis by regulating apoptosis

Mazelin, Laetitia; Bernet, Agnès; Bonod‐Bidaud, Christelle; Pays, Laurent; Arnaud, Ségolène; Gespach, Christian; Bredesen, Dale E.; Scoazec, Jean‐Yves; Mehlen, Patrick

doi:10.1038/nature02788

Cited by 265 publications

(274 citation statements)

References 19 publications

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“…In support of this model, it has recently been shown that transgenic mice that overexpress netrin-1 in the intestine develop spontaneous intestinal tumors. 160 However, an overexpression of netrin in or around human tumors has not been reported yet. As for semaphorins and slits, another possible function of netrins in cancer could be to regulate angiogenesis.…”

Section: Netrins and Their Receptorsmentioning

confidence: 98%

The brain within the tumor: new roles for axon guidance molecules in cancers

2005

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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.

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Section: Netrins and Their Receptorsmentioning

confidence: 98%

The brain within the tumor: new roles for axon guidance molecules in cancers

2005

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“…There is now accumulating evidence with regard to netrin-1 to support this idea. Indeed, forced expression of netrin-1 in the digestive tract of transgenic mice has been associated with decreased apoptosis in the intestine, development of advanced adenomas and tumor progression to adenomacarcinoma in a setting of adenoma predisposition (Mazelin et al, 2004). More recently, high levels of netrin-1 were detected in a large panel of human cancers from distinct organs, and netrin-1 overexpression was correlated with a blocking of the proapoptotic functions of netrin-1 receptors.…”

Section: Drs Are Altered During Tumor Progressionmentioning

confidence: 99%

Dependence receptors: a new paradigm in cell signaling and cancer therapy

2010

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Dependence receptors (DRs) now form a family of more than a dozen membrane receptors that are not linked by their structure, but by common functional traits. The most notable is their ability to trigger two opposite signaling pathways: in the presence of ligand, these receptors activate classic signaling pathways implicated in cell survival, migration and differentiation. In the absence of ligand, they do not stay inactive, rather they elicit an apoptotic signal. Thus, cells expressing this kind of receptor are dependent on the presence of ligand in the extracellular environment to survive. This review will recapitulate the increasing data regarding the molecular mechanisms associated with DRs, their potential implication during development, as well as their deregulation during tumorigenesis and, finally, their emergence as new possible therapeutic targets for cancer treatment.

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“…64 Integrins require an immobilized substrate ligand (or other tensional force) to promote sustained signaling and cytoskeletal remodeling. Thus, although the presence of a soluble netrin may be sufficient to promote survival of cells expressing the dependence receptor DCC, 65 soluble integrin ligands are generally insufficient to maintain cell survival, and instead tend to act as antagonists which prevent engagement of substrate ligands, thus promoting integrin-mediated death.…”

Section: Antagonized Integrins Promote Apoptosis Of Adherent Cellsmentioning

confidence: 99%

Integrins as a distinct subtype of dependence receptors

Stupack

2005

Cell Death Differ

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In the absence of their cognate ligand, dependence receptors trigger programmed cell death. This function is the defining feature of dependence receptors, which include members of several different protein families. The integrins are a family of heterodimeric receptors for extracellular matrix (ECM) proteins, mediating cell anchorage and migration. Integrins share characteristics with dependence receptors, and integrin binding to substrate ECM ligands is essential for cell survival. Although integrins do not conform in all characteristics to the established definitions of dependence receptors, alterations in the expression of integrins and their ligands during physiological and pathological events, such as wound healing, angiogenesis and tumorigenesis, do regulate cell fate in a ligand-dependent manner. This biosensory function of integrins fits well with our current concept of dependence receptor action, and thus integrins may rightly be considered to comprise a distinct subclass of dependence receptor.

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Netrin-1 controls colorectal tumorigenesis by regulating apoptosis

Cited by 265 publications

References 19 publications

The brain within the tumor: new roles for axon guidance molecules in cancers

The brain within the tumor: new roles for axon guidance molecules in cancers

Dependence receptors: a new paradigm in cell signaling and cancer therapy

Integrins as a distinct subtype of dependence receptors

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