Apoptosis of adherent cells by recruitment of caspase-8 to unligated integrins

Stupack, Dwayne G.; Puente, Xosé S.; Boutsaboualoy, Souphaphone; Storgard, Chris; Cheresh, David A.

doi:10.1083/jcb.200106070

Cited by 503 publications

(421 citation statements)

References 67 publications

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“…These 'non-liganded integrins,' which are either unligated or occupied with a soluble antagonist, not only disrupt survival signaling but also actively induce apoptosis, hence supporting the view of integrins as DRs (Stupack et al, 2001) (Figure 2 and Table 1).…”

Section: Dependence Receptors: a Short Historymentioning

confidence: 55%

“…Indeed, Stupack et al (2001) elegantly showed that integrins, as DRs, trigger apoptosis through recruitment of caspase 8.…”

Section: Proapoptotic Signaling By Drsmentioning

confidence: 99%

“…These receptors are named 'dependence receptors.' To date, the dependence receptor (DR) family is composed of more than a dozen members including DCC (deleted in colorectal carcinoma) (Mehlen et al, 1998), UNC5Hs (uncoordinated 5 homologs), neogenin (Matsunaga et al, 2004), p75 NTR (p75 neurotrophin receptor) (Rabizadeh et al, 1993), RET (rearranged during transfection) (Bordeaux et al, 2000), TrkC (tyrosine kinase receptor C) (Tauszig-Delamasure et al, 2007), Ptc (patched) (Thibert et al, 2003), EphA4 (ephrin type A receptor 4) (Furne et al, 2009), ALK (anaplastic lymphoma kinase) (Mourali et al, 2006), MET (Tulasne et al, 2004) and some integrins (Stupack et al, 2001). All of them are involved in both nervous system development and cancer progression.…”

mentioning

confidence: 99%

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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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Section: Dependence Receptors: a Short Historymentioning

confidence: 55%

“…Indeed, Stupack et al (2001) elegantly showed that integrins, as DRs, trigger apoptosis through recruitment of caspase 8.…”

Section: Proapoptotic Signaling By Drsmentioning

confidence: 99%

mentioning

confidence: 99%

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

2010

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“…In fact, apoptosis does occur under these circumstances. 15,[58][59][60] Cell surface expression of integrins in the antagonized 60 or unligated state 58 can promote apoptosis among otherwise attached and 'spread' cells.…”

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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“…In cells in which most of the integrins are ligated, pro-survival signals were reported whereas pro-apoptotic signals were found in unligated cells [50,51]. The role of heparin in this complex network will be addressed in future studies.…”

Section: Discussionmentioning

confidence: 99%