Integrins as a distinct subtype of dependence receptors

Stupack, Dwayne G.

doi:10.1038/sj.cdd.4401658

Cited by 82 publications

(56 citation statements)

References 114 publications

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“…This controversy is further supported by the genetic identification in Drosophila melanogaster of an ALK ligand, jelly belly (jeb), which has no similarities with pleiotrophin or midkine Loren et al, 2003). Finally, in the particular case of integrins, the ligand must be an immobilized substrate ligand to block apoptosis as, contrary to other DRs, soluble ligand is not sufficient to counteract cell death induction (Stupack, 2005).…”

Section: Role Of Ligand Bindingmentioning

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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Section: Role Of Ligand Bindingmentioning

confidence: 99%

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

2010

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“…7 We will end this special issue with a review by Dwayne Stupack, who will describe a recently identified set of dependence receptors, integrins. 8 As usual, the reading of these reviews will raise more questions than they actually answer. What is the relation between integrins and DCC, molecules that do not display much sequence similarity?…”

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confidence: 99%

The dependence receptor notion: another way to see death

Mehlen

2005

Cell Death Differ

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It has been known for over half a century that cells depend for their survival on stimulation that is mediated by various receptors and sensors. For example, cells may require specific soluble trophic factors, cytokines, hormones, extracellular matrix interactions, cell-cell interactions, or electrical activity for survival. In each case, withdrawal of the stimulus leads to apoptosis. It has generally been assumed that this occurs through the loss of the associated positive survival signals, such as Akt phosphorylation. While such survival signals are clearly very important, data obtained over the past 10 years argue for a complementary and novel form of signal transduction, which induces apoptosis and is activated by stimulus withdrawal. This 'negative signal transduction' is mediated by specific 'dependence receptors', which induce apoptosis only in the absence of the required stimulus (e.g. when unbound by a trophic ligand). Thus, the expression of various dependence receptors creates states of dependence on their respective ligands.From a very dubitative -and should we confess, sometimes aggressive -attitude towards this notion, for example, (i) 'how dare you even think that an unbound receptor could be active', (ii) 'everything about cell death following trophic factor withdrawal is known: a default program due to kinasesdependent pathways being shut off', or (iii) 'your data are simple artifacts of cell culture and protein overexpression' -we are slowly moving towards a more respectable view, maybe. The reason for this gain of interest is clearly due to the fact that from pure in vitro studies using immortalized cells, 1,2 this notion has recently been supported by studies in animals models. 3,4 However, there are many ramifications to the dependence receptor theory: for example, the expression of dependence receptors ties cells to a specific context, in which the ligand is available, and therefore may serve to block metastatic spread of neoplasms or growth beyond local ligand availability. Another example of the effects of dependence receptors is the mediation of developmental cell death in cells that do not receive trophic factor support. Therefore, dependence receptors often play a dual role, both as tumor suppressors and mediators of neuronal development. Indeed, the vast majority of the dependence receptors isolated so far has been shown to be involved in neuronal navigation and in the regulation of cancer progression. This special issue will deal with the different aspects of the duality of dependence receptors. Firstly, Dale E Bredesen and colleagues will present an overview of the notion of dependence receptors and discuss the nature of the different dependence receptors isolated so far. 5 They will review what is known about the mechanisms these receptors use to trigger cell death, and how this implicates them in nervous system development, cancer progression, and neurodegenerative diseases. Hirofumi Arakawa will then sign an exciting review on a specific set of dependence receptors, the netrin-1 ...

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“…• mechanotransduction -a process of converting mechanical stimuli such as press or stretching to intracellular signals resulting in a specific gene expression, • regulation of vasomotor response: contraction (integrins α1β1 and α5β1) and relaxation (integrin αvβ3) of the vessel [15], • regulation of vessel permeability by modification of cadherins in endothelial adherent junctions and by contraction of collagen fibers in ECM (integrin α2β1) [20], • regulation of VSMCs tensegrity (resting tension in VSMC triggered by external mechanical forces, which influences myocyte behavior) [17], • activation of the cell death program [24]; integrins belong to a group of dependence receptors which lack of activity can lead to cell apoptosis, • modulation of cells shape by linkage with cytoskeletal actin and reorganization of actin filaments. In VSMCs, there are 13 combinations of integrins: α1β1, α2β1, α3β1, α4β1, α5β1, α6β1, α7β1, α8β1, α8β1, αVβ1, αVβ3, αVβ5, α6β4 [15,16].…”

Section: Introductionmentioning

confidence: 99%