title: Fas and TRAIL 'death receptors' as initiators of inflammation: Implications for cancer.
abstract: Fas (CD95/APO-1) and TRAIL (CD253, TNFSF10, APO2) are members of a subset of the TNF receptor superfamily known as 'death receptors'. To date, the overwhelming majority of studies on Fas and TRAIL (TNF-related apoptosis-inducing ligand) have explored the role of these receptors as initiators of apoptosis. However, sporadic reports also suggest that engagement of the Fas and TRAIL receptors can lead to other outcomes such as cytokine and chemokine production, cell proliferation, cell migration and differentiation. Indeed, although transformed cells frequently express Fas and TRAIL, most do not undergo apoptosis upon engagement of these receptors and significant effort has been devoted toward exploring how to sensitize such cells to the pro-apoptotic effects of 'death receptor' stimulation. Moreover, the expression of Fas and TRAIL receptors is greatly elevated in many cancer types such as hepatocellular carcinoma, renal carcinoma and ovarian cancer, suggesting that such tumors benefit from the expression of these receptors. Furthermore, several studies have shown that tumor proliferation, progression and invasion can be impaired through blocking or downregulation of Fas expression, but the mechanistic basis for these effects is largely unknown. Thus, the characterization of Fas and TRAIL as 'death receptors' is a gross oversimplification, especially in the context of cancer. It is becoming increasingly clear that 'death receptor' engagement can lead to outcomes, other than apoptosis, that become subverted by certain tumors to their benefit. Here we will discuss death-independent outcomes of Fas and TRAIL signaling and their implications for cancer.
authors: Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland.
authors: Sean P
authors: SP
authors: Cullen
authors: Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland. Electronic address: martinsj@tcd.ie.
authors: Seamus J
authors: SJ
authors: Martin
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism; D053218:Receptors, Death Domain / Q000378:metabolism*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
chemical_list: D016207:Cytokines; D053218:Receptors, Death Domain; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand
keywords: Cancer; Cytokines; Death receptors; Fas; Inflammation; TRAIL