The prognostic significance of overexpression of the decoy receptor for Fas ligand (DcR3) in patients with gastric carcinomas

Takahama, Yasushi; Yamada, Yoshiaki; Emoto, Koji; Fujimoto, Heisuke; Takayama, Tomoyoshi; Ueno, Masayoshi; Uchida, Hideki; Hirao, Shuya; Mizuno, Takashi; Nakajima, Yoshiyuki

doi:10.1007/s101200200011

Cited by 71 publications

(57 citation statements)

References 44 publications

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“…The overexpression of DcR3 can be found in multiple human malignant tumors such as gastric carcinoma (Takahama et al, 2002), colon carcinoma , esophageal carcinoma (Li et al, 2005), lung carcinoma (Pitti et al, 1998), hepatic carcinoma Chen and Luo, 2008), spongioblastoma (Arakawa et al, 2005), oophoroma (Connor and Felder, 2008;Anderson et al, 2010), etc. Research has found that both the gene level and protein level of DcR3 in tumor tissues are over-expressed whereas those in normal tissues surrounding tumor are hardly.…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of Expression and Amplification of the DcR3 Gene in Pancreatic Carcinomas

Zhou

Song²,

Li³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Section: Discussionmentioning

confidence: 99%

Clinical Significance of Expression and Amplification of the DcR3 Gene in Pancreatic Carcinomas

Zhou

Song²,

Li³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…9 In addition, the soluble and non-signaling decoy receptor (DcR3) provides a mechanism for malignant cells to evade CD95 ligand-induced apoptosis in certain tumors and it was shown that elevated DcR3 expression can be used as a prognostic marker for survival of cancer patients. 10,11 The value of other caspase-regulating factors as prognostic markers has also been analyzed. In particular, downregulation of the mitochondrial IAP antagonist Smac/DIABLO is associated with renal cell carcinomas, and overexpression of survivin, another IAP, has been observed in most transformed cell lines and cancers tested to date, as compared with its absence in most normal adult tissues.…”

Section: Apoptosis As a Defense Strategy Against Tumorogenesismentioning

confidence: 99%

Caspases and cancer

2011

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Evasion of apoptosis is considered to be one of the hallmarks of human cancers. This cell death modality is executed by caspases and several upstream regulatory factors, which direct their proteolytic activity, have been defined as either tumor suppressors or oncogenes. Often these regulatory factors, in addition to being potent apoptosis inducers, function in cell survival or repair signaling pathways in response to cellular stress. Thus, loss of function in a distinct regulatory mechanism does not necessarily mean that tumor formation is due to apoptosis malfunction resulting from insufficient caspase activation. Although each caspase has been assigned a distinct role in apoptosis, some redundancy with respect to their regulatory functions and substrate recognition is evident. Jointly, these proteases could be considered to possess solid tumor suppressor function, but what is the evidence that deregulation of specific caspases per se induces inappropriate cell survival, leading to enhanced tumorigenic potential? This question will be addressed in this review, which covers basic molecular mechanisms derived from in vitro analyses and emphasizes new insights that have emerged from in vivo and clinical studies. In organisms, excess cells during development, as well as potentially harmful cells resulting from pathophysiological conditions, are eliminated by various cell death modalities. Among them, apoptosis is the most investigated, and almost 40 years ago, it was described as a major defense strategy that prevents cells from acquiring tumorigenic potential. 1 This suicide mechanism is controlled by multiple and interrelated pathways ensuring that caspases, the proteolytic initiators and executioners of apoptosis, are triggered only in cells requiring termination. There is overwhelming experimental evidence supporting the idea that disturbances in the regulation of caspase activation are central for the avoidance of cancer cell death, both in vitro and in vivo. However, what evidences suggest that caspases per se act as tumor suppressors? It was reported that cells do not necessarily undergo caspaseindependent cell death in the absence of active caspases, but may instead survive insult and even promote clonogenic tumor growth. 2 Yet, it was unclear which individual caspases could fulfill this function. Recently, certain initiator caspases have been suggested as putative tumor suppressor genes. 3,4 This review is focusing on caspases and their role in tumor suppression, and emphasizing new evidences that have emerged from in vivo observations and clinical material, taking into consideration supporting in vitro data that has enlightened basic molecular mechanisms. CaspasesClassification of human caspases is based either on their function, the size of their pro-domain or cleavage specificity.Considering the first criteria, caspase-1, -4 and -5 belong to the group I (inflammatory) caspases that are involved in cytokine maturation. These proteases are primarily associated with the innate immunity against pathogens an...

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“…DcR3 sequesters and inactivates membrane-bound Fas ligand on adjacent cells and infiltrating tumour cells and prevents activation of Fas receptor. Patients with gastrointestinal tract carcinomas that overexpress DcR3 have a significantly shortened mean duration of survival than patients with tumours expressing normal levels of DcR3 [62]. Human keratinocytes overexpress DcR3, and expression is rapidly decreased in cells following ultraviolet B irradiation [63].…”

Section: Modulators Of Disc Formationmentioning

confidence: 99%