Cyr61 is a potential prognostic marker for prostate cancer

Article (PDF Available)inAsian Journal of Andrology 14(3):405-8 · February 2012with22 Reads
DOI: 10.1038/aja.2011.149 · Source: PubMed
Cysteine-rich angiogenic inducer 61 (Cyr61) is an extracellular matrix protein involved in the transduction of growth factor and hormone signaling that is frequently altered in expression in several types of cancers. In prostate cancer (PCa), Cyr61 is highly expressed in organ-confined disease. Further, Cyr61 expression levels are associated with a lower risk of disease recurrence, and can be quantitatively measured in the serum. Considered together, these results indicate that Cyr61 is a potential and clinically useful tissue, as well as serum-based biomarker for differentiating lethal and non-lethal PCa.


    • "Differences between P-BE and nonP-BE are thus more significant at t0. This phenomenon of increased expression on localized benign disease and a decreased expression upon progression to metastasis is known to occur in several contexts such as for CYR61 in prostate cancer (reviewed in [70]). While no mechanistic explanation justifies yet this observation in BE, it is possible that, as in prostate, CYR61 and TAZ are more important in the neoplastic initiation than progression. "
    [Show abstract] [Hide abstract] ABSTRACT: Barrett's esophagus is the major risk factor for esophageal adenocarcinoma. It has a low but non-neglectable risk, high surveillance costs and no reliable risk stratification markers. We sought to identify early biomarkers, predictive of Barrett's malignant progression, using a meta-analysis approach on gene expression data. This in silico strategy was followed by experimental validation in a cohort of patients with extended follow up from the Instituto Português de Oncologia de Lisboa de Francisco Gentil EPE (Portugal). Bioinformatics and systems biology approaches singled out two candidate predictive markers for Barrett's progression, CYR61 and TAZ. Although previously implicated in other malignancies and in epithelial-to-mesenchymal transition phenotypes, our experimental validation shows for the first time that CYR61 and TAZ have the potential to be predictive biomarkers for cancer progression. Experimental validation by reverse transcriptase quantitative PCR and immunohistochemistry confirmed the up-regulation of both genes in Barrett's samples associated with high-grade dysplasia/adenocarcinoma. In our cohort CYR61 and TAZ up-regulation ranged from one to ten years prior to progression to adenocarcinoma in Barrett's esophagus index samples. Finally, we found that CYR61 and TAZ over-expression is correlated with early focal signs of epithelial to mesenchymal transition. Our results highlight both CYR61 and TAZ genes as potential predictive biomarkers for stratification of the risk for development of adenocarcinoma and suggest a potential mechanistic route for Barrett's esophagus neoplastic progression.
    Full-text · Article · Sep 2016
    • "CYR61 can also play a role in the proliferation , invasion, survival, and metastasis of cancer cells [7]. Clinically, CYR61 expression is related to the prognosis of prostate cancer or breast cancer [8], although little is known about the role of CYR61 in colorectal cancer. Jeong et al. [9] measured CYR61 expression in 251 specimens from patients with colorectal cancer; in 6 cell lines (HT29, colo205, Lovo, HCT116, SW480, and SW620); and in 20 pairs of normal vs. colorectal cancer tissues. "
    [Show abstract] [Hide abstract] ABSTRACT: Purpose: One of the features in cancer development is the migration of cancer cells to form metastatic lesions. CYR61 protein promotes migration and the epithelial-mesenchymal transition in several cancer cell types. Evidence suggests that CYR61 and dexamethasone are relevant to colorectal cancer. However, relationships between them and colorectal cancer are still unclear. Understanding the molecular mechanism of colorectal cancer progression related with CYR61 and dexamethasone, which is widely used for combination chemotherapy, is necessary for improved therapy. Materials and methods: We used colorectal cancer cells, HCT116, co-treated with TGF-β1 and dexamethasone to examine the inhibitory migration effect of dexamethasone by migratory assay. Alternatively, both migratory pathways, expression of AKT and ERK, and the target factor CYR61 was also tested by co-treatment with TGF and dexamethasone. Results: We report that dexamethasone significantly inhibited TGF-β1-induced cell migration, without affecting cell proliferation. Importantly, we observed that TGF-β1 promoted the EMT process and that dexamethasone co-treatment abolished this effect. ERK and AKT signaling pathways were found to mediate TGF-β1-induced migration, which was inhibited by dexamethasone. In addition, TGF-β1 treatment induced CYR61 expression whereas dexamethasone reduced it. These observations were compatible with the modulation of migration observed following treatment of HCT116 cells with human recombinant CYR61 and anti-CYR61 antibody. Our results also indicated that TGF-β1 enhanced collagen I and reduced matrix metalloproteinase 1 expression, which was reversed by dexamethasone treatment. Conclusion: These findings suggested that dexamethasone inhibits AKT and ERK phosphorylation, leading to decreased CYR61 expression, which in turn blocks TGF-β1-induced migration.
    Full-text · Article · Dec 2015
    • "The expression of each of the four candidate genes have been reported to be dysregulated in cancer, and correlated with cancer progression. A loss of expression of TGFBR1 and CYR61 has been associated with prostate cancer progression and/or recurrence among many other cancer types31323334. Data from our methylation array showed that the promoter regions of TGFBR1 and CYR61 were hypermethylated in LnCAP cells (Fig. 6B and data not shown). "
    [Show abstract] [Hide abstract] ABSTRACT: Epigenetic changes, including aberrant DNA methylation, result in altered gene expression and play an important role in carcinogenesis. Phytochemicals such as sulforaphane (SFN) and 3,3'-diindolylmethane (DIM) are promising chemopreventive agents for the treatment of prostate cancer. Both have been shown to induce re-expression of genes, including tumor suppressor genes silenced in cancer cells, via modulation of epigenetic marks including DNA methylation. However, it remained unclear the effects SFN and DIM on DNA methylation at a genomic scale. The goal of this study was to determine the genome-wide effects of SFN and DIM on promoter methylation in normal prostate epithelial cells and prostate cancer cells. Both SFN and DIM treatment decreased DNA methyltransferase expression in normal prostate epithelial cells (PrEC), and androgen-dependent (LnCAP) and androgen-independent (PC3) prostate cancer cells. The effects of SFN and DIM on promoter methylation profiles in normal PrEC, LnCAP and PC3 prostate cancer cells were determined using methyl-DNA immunoprecipitation followed by genome-wide DNA methylation array. We showed widespread changes in promoter methylation patterns, including both increased and decreased methylation, in all three prostate cell lines in response to SFN or DIM treatments. In particular, SFN and DIM altered promoter methylation in distinct sets of genes in PrEC, LnCAP, and PC3 cells, but shared similar gene targets within a single cell line. We further showed that SFN and DIM reversed many of the cancer-associated methylation alterations, including aberrantly methylated genes that are dysregulated or are highly involved in cancer progression. Overall, our data suggested that both SFN and DIM are epigenetic modulators that have broad and complex effects on DNA methylation profiles in both normal and cancerous prostate epithelial cells. Results from our study may provide new insights into the epigenetic mechanisms by which SFN and DIM exert their cancer chemopreventive effects.
    Full-text · Article · Jan 2014
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