Expression of Fas ligand is an early event in colorectal carcinogenesis

Shimoyama, Masaaki; Kanda, Tatsuo; Liu, Huan; Koyama, Yu; Suda, Takeyasu; Sakai, Yasuo; Hatakeyama, Katsuyoshi

doi:10.1002/1096-9098(200101)76:1<63::aid-jso1011>3.0.co;2-c

Cited by 20 publications

(8 citation statements)

References 19 publications

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“…High FASLG expression in the CRC patients complies with previous clinical observations [6], [17] in which high FASLG expression was correlated with high incidences of metastases and poor survival in colorectal carcinoma patients and in other carcinoma patients.…”

Section: Resultssupporting

confidence: 89%

Pathway-Based Evaluation in Early Onset Colorectal Cancer Suggests Focal Adhesion and Immunosuppression along with Epithelial-Mesenchymal Transition

Nam

Park

2012

PLoS ONE

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Colorectal cancer (CRC) has one of the highest incidences among all cancers. The majority of CRCs are sporadic cancers that occur in individuals without family histories of CRC or inherited mutations. Unfortunately, whole-genome expression studies of sporadic CRCs are limited. A recent study used microarray techniques to identify a predictor gene set indicative of susceptibility to early-onset CRC. However, the molecular mechanisms of the predictor gene set were not fully investigated in the previous study. To understand the functional roles of the predictor gene set, in the present study we applied a subpathway-based statistical model to the microarray data from the previous study and identified mechanisms that are reasonably associated with the predictor gene set. Interestingly, significant subpathways belonging to 2 KEGG pathways (focal adhesion; natural killer cell-mediated cytotoxicity) were found to be involved in the early-onset CRC patients. We also showed that the 2 pathways were functionally involved in the predictor gene set using a text-mining technique. Entry of a single member of the predictor gene set triggered a focal adhesion pathway, which confers anti-apoptosis in the early-onset CRC patients. Furthermore, intensive inspection of the predictor gene set in terms of the 2 pathways suggested that some entries of the predictor gene set were implicated in immunosuppression along with epithelial-mesenchymal transition (EMT) in the early-onset CRC patients. In addition, we compared our subpathway-based statistical model with a gene set-based statistical model, MIT Gene Set Enrichment Analysis (GSEA). Our method showed better performance than GSEA in the sense that our method was more consistent with a well-known cancer-related pathway set. Thus, the biological suggestion generated by our subpathway-based approach seems quite reasonable and warrants a further experimental study on early-onset CRC in terms of dedifferentiation or differentiation, which is underscored in EMT and immunosuppression.

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Section: Resultssupporting

confidence: 89%

Pathway-Based Evaluation in Early Onset Colorectal Cancer Suggests Focal Adhesion and Immunosuppression along with Epithelial-Mesenchymal Transition

Nam

Park

2012

PLoS ONE

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“…In these factors, Fas and FasL have been regarded as very important effectors of apoptosis in various biological conditions and its disregulated expression in a variety of carcinomas such as breast [42], hepatocellular [43], colorectal [44], and nasopharyngeal [45] carcinoma. Fas (CD95 or APO-1) [46], is a 36-kDa cell surface protein that belongs to the death receptor (DR) family.…”

Section: Discussionmentioning

confidence: 99%

Emodin induces apoptosis of human cervical cancer hela cells via intrinsic mitochondrial and extrinsic death receptor pathway

et al. 2013

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BackgroundEmodin is a natural anthraquinone derivative isolated from the Rheum palmatum L. Aim: The aim of the present study was to investigate the effect of emodin on the apoptosis of the human cervical cancer line HeLa and to identify the mechanisms involved.MethodsRelative cell viability was assessed by MTT assay after treatment with emodin. Cell apoptosis was detected with TUNEL, Hoechst 33342 staining and quantified with flow cytometry using annexin FITC-PI staining.ResultsThe percentage of apoptotic cells was 0.8, 8.2, 22.1, and 43.7%, respectively. The mRNA levels of Caspase-9, -8 and −3 detected by Real-time PCR after treatment with emodin were significantly increased. Emodin increased the protein levels of Cytochome c, Apaf-1, Fas, FasL, and FADD but decreased the protein levels of Pro-caspase-9, Pro-caspase-8 and Pro-caspase-3.ConclusionWe conclude that the emodin inhibited HeLa proliferation by inducing apoptosis through the intrinsic mitochondrial and extrinsic death receptor pathways.

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“…Two patterns of FasL expression on carcinoma cells have been shown by immunohistochemical staining: (1) up-regulation of FasL expression on carcinoma is positively associated with clinicopathological features in patients, shown by that FasL expression is an early event in epithelial cell transformation (adenoma), followed by an increase in the percentage of FasL-expressing carcinoma cells in high-stage or -grade lesions, and the poorer survival of patients with high levels of FasL expression (Table 2); and (2) high levels of FasL expression have been seen as an independent factor for clinicopathological features, indicated by the positive staining of persistent FasL expression regardless of tumor stage, histologic grade, invasion and metastasis in many studies [47,58-61]. All of these observations suggest that FasL expression is critical for carcinoma survival by induction of TIC apoptosis.…”

Section: Introductionmentioning

confidence: 99%

The immunoregulatory mechanisms of carcinoma for its survival and development

Wang

2011

J Exp Clin Cancer Res

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The immune system in patients detects and eliminates tumor cells, but tumors still progress persistently. The mechanisms by which tumor cells survive under the pressure of immune surveillance are not fully understood. This review is to present the evidence from clinical studies, showing a significant correlation of clinicopathological features of carcinoma with: (1) the loss of classical human leukocyte antigen class I, (2) the up-regulation of non-classical human leukocyte antigen class I, pro-apoptotic Fas ligand and receptor-binding cancer antigen expressed on SiSo cells I, and (3) the formation of immunosuppressive microenvironment by up-regulation of transforming growth factor-beta, Galectin-1, inhibitory ligand B7s, indoleamine 2,3-dioxygenase and arginase, as well as by recruitment of tumor-induced myeloid-derived suppressor cells and regulatory T cells. All of these factors may together protect carcinoma cells from the immune-cytotoxicity.

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Expression of Fas ligand is an early event in colorectal carcinogenesis

Abstract: FasL expression is commonly observed not only in cancer but also in highly dysplastic tissue. These observations suggest that FasL expression may be an important event in the transformation process leading to adenocarcinoma.

Cited by 20 publications

References 19 publications

Pathway-Based Evaluation in Early Onset Colorectal Cancer Suggests Focal Adhesion and Immunosuppression along with Epithelial-Mesenchymal Transition

Pathway-Based Evaluation in Early Onset Colorectal Cancer Suggests Focal Adhesion and Immunosuppression along with Epithelial-Mesenchymal Transition

Emodin induces apoptosis of human cervical cancer hela cells via intrinsic mitochondrial and extrinsic death receptor pathway

The immunoregulatory mechanisms of carcinoma for its survival and development

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