Clinicopathological Significance of Caspase-8 and Caspase-10 Expression in Rectal Cancer

Xu, Bing; Zhou, Zong‐Guang; Li, Yuan; Wang, Ling; Yang, Lie; Zhou, Bin; Liu, Hai-Yi; Song, Junmin; Zeng, Yujian; Wang, Rong; Shen, Xiaogang; Sun, Xiao‐Feng

doi:10.1159/000151392

Cited by 18 publications

(19 citation statements)

References 59 publications

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“…For example, we observed that the pro-apoptotic gene CASP10 was strongly down regulated early after stimulation with LPS, exclusively in humans (Figure S7). Somatic mutations in CASP10 , as well as reduced expression levels of this gene, were found to be associated with a number of different human cancers [41]–[44]. The observed inter-species differences in the regulation of CASP10 following infection may therefore be related to differences in the rates of cancer across species.…”

Section: Discussionmentioning

confidence: 99%

Functional Comparison of Innate Immune Signaling Pathways in Primates

et al. 2010

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Humans respond differently than other primates to a large number of infections. Differences in susceptibility to infectious agents between humans and other primates are probably due to inter-species differences in immune response to infection. Consistent with that notion, genes involved in immunity-related processes are strongly enriched among recent targets of positive selection in primates, suggesting that immune responses evolve rapidly, yet providing only indirect evidence for possible inter-species functional differences. To directly compare immune responses among primates, we stimulated primary monocytes from humans, chimpanzees, and rhesus macaques with lipopolysaccharide (LPS) and studied the ensuing time-course regulatory responses. We find that, while the universal Toll-like receptor response is mostly conserved across primates, the regulatory response associated with viral infections is often lineage-specific, probably reflecting rapid host–virus mutual adaptation cycles. Additionally, human-specific immune responses are enriched for genes involved in apoptosis, as well as for genes associated with cancer and with susceptibility to infectious diseases or immune-related disorders. Finally, we find that chimpanzee-specific immune signaling pathways are enriched for HIV–interacting genes. Put together, our observations lend strong support to the notion that lineage-specific immune responses may help explain known inter-species differences in susceptibility to infectious diseases.

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Section: Discussionmentioning

confidence: 99%

Functional Comparison of Innate Immune Signaling Pathways in Primates

et al. 2010

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“…There is evidence of increased expression of caspase-8 in several types of cancer including colorectal and rectal, gastric, pancreatic, and breast cancers [13], [14]–[17]. Besides, it has been also shown that caspase-8 expression is lost or inactivated in certain types of cancer such as small cell lung cancer, neuroblastoma, gastric carcinoma and hepatocellular carcinoma [18]–[25].…”

Section: Introductionmentioning

confidence: 99%

Analysis of Death Receptor 5 and Caspase-8 Expression in Primary and Metastatic Head and Neck Squamous Cell Carcinoma and Their Prognostic Impact

et al. 2010

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Death receptor 5 (DR5) and caspase-8 are major components in the extrinsic apoptotic pathway. The alterations of the expression of these proteins during the metastasis of head and neck squamous cell carcinoma (HNSCC) and their prognostic impact have not been reported. The present study analyzes the expression of DR5 and caspase-8 by immunohistochemistry (IHC) in primary and metastatic HNSCCs and their impact on patient survival. Tumor samples in this study included 100 primary HNSCC with no evidence of metastasis, 100 primary HNSCC with lymph node metastasis (LNM) and 100 matching LNM. IHC analysis revealed a significant loss or downregulation of DR5 expression in primary tumors with metastasis and their matching LNM compared to primary tumors with no evidence of metastasis. A similar trend was observed in caspase-8 expression although it was not statistically significant. Downregulation of caspase-8 and DR5 expression was significantly correlated with poorly differentiated tumors compared to moderately and well differentiated tumors. Univariate analysis indicates that, in HNSCC with no metastasis, higher expression of caspase-8 significantly correlated with better disease-free survival and overall survival. However, in HNSCC with LNM, higher caspase-8 expression significantly correlated with poorer disease-free survival and overall survival. Similar results were also generated when we combined both DR5 and caspase-8. Taken together, we suggest that both DR5 and caspase-8 are involved in regulation of HNSCC metastasis. Our findings warrant further investigation on the dual role of caspase-8 in cancer development.

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“…Caspase-8, caspase-10 and caspase-9 are believed to be the initiator caspases at the top of the caspase signalling cascade (46,47). It has been recently reported that caspase-10 expression is downregulated in both rectal adenomas and cancers and may be involved in the pathogenesis of rectal cancer (48). Thus, we surmised that the increased expression of caspase-10 might play a key role in curcumin-induced A549 cell apoptosis.…”

Section: Discussionmentioning

confidence: 85%

Curcumin promotes apoptosis in human lung adenocarcinoma cells through miR-186* signaling pathway

Zhang

Du²,

Wu³

et al. 2010

Oncol Rep

118

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Abstract. Lung cancer is one of the leading causes of cancerrelated death worldwide. Curcumin has been reported to have an antitumor effect by inducing apoptosis and suppressing growth of tumor cells. However, the mechanism by which curcumin exerts its anti-cancer effect needs further research. The purpose of the present study was to identify a miRNAmediated mechanism which plays a role in the anti-cancer effects of curcumin. Alterations in miRNA expression were seen in curcumin-treated A549 cells, including significant downregulation of miRNA-186 * expression by microarray analysis and real-time PCR. The miRNA-186 * functions by overexpression or inhibition were investigated using biological assays in A549 cells. Additionally, caspase-10 was identified as a target of miRNA-186 * using dual luciferase reporter assays and Western blot analysis. These results demonstrate that curcumin induces A549 cell apoptosis through a miRNA pathway. Also, miRNA-186 * could serve as a potential gene therapy target in curcumin treatment. Furthermore, caspase-10 was shown to be a target of miR-186 * regulation.

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Clinicopathological Significance of Caspase-8 and Caspase-10 Expression in Rectal Cancer

Cited by 18 publications

References 59 publications

Functional Comparison of Innate Immune Signaling Pathways in Primates

Functional Comparison of Innate Immune Signaling Pathways in Primates

Analysis of Death Receptor 5 and Caspase-8 Expression in Primary and Metastatic Head and Neck Squamous Cell Carcinoma and Their Prognostic Impact

Curcumin promotes apoptosis in human lung adenocarcinoma cells through miR-186* signaling pathway

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