NT5E and FcGBP as key regulators of TGF-1-induced epithelial–mesenchymal transition (EMT) are associated with tumor progression and survival of patients with gallbladder cancer

Li, Xiong; Wen, Yu; Miao, Xiangshui; Yang, Zhulin

doi:10.1007/s00441-013-1752-1

Cited by 121 publications

(104 citation statements)

References 24 publications

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“…Our study is thus consistent with recent reports that in the tumor microenvironment, CAFs are important regulators of tumor immunity (38). Another finding of our study is the observation that CD73 gene expression is strongly correlated with an EMT gene signature, consistent with a recent study in gallbladder cancer cells (18). CD73 has been shown to be upregulated on human mammary epithelial cells stably expressing the EMT-inducers Twist, Snail, or TGFb1 (39).…”

Section: Discussionsupporting

confidence: 93%

“…Others have shown that in vitro treatment of alloantigenprimed human T cells with an anti-CD73 mAb enhances T-cell cytotoxicity against human ovarian cancer cells (16). CD73 overexpression has been associated with worse clinical outcomes in different types of cancer (15,(17)(18)(19). In triple negative breast cancer, high levels of CD73 gene expression are associated with poor prognosis and resistance to immunogeniccell death induced by anthracyclines (15).…”

Section: Introductionmentioning

confidence: 99%

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CD73 Is Associated with Poor Prognosis in High-Grade Serous Ovarian Cancer

et al. 2015

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The cell surface nucleotidase CD73 is an immunosuppressive enzyme involved in tumor progression and metastasis. Although preclinical studies suggest that CD73 can be targeted for cancer treatment, the clinical impact of CD73 in ovarian cancer remains unclear. In this study, we investigated the prognostic value of CD73 in high-grade serous (HGS) ovarian cancer using gene and protein expression analyses. Our results demonstrate that high levels of CD73 are significantly associated with shorter diseasefree survival and overall survival in patients with HGS ovarian cancer. Furthermore, high levels of CD73 expression in ovarian tumor cells abolished the good prognosis associated with intraepithelial CD8 þ cells. Notably, CD73 gene expression was highest in the C1/stromal molecular subtype of HGS ovarian cancer and positively correlated with an epithelial-to-mesenchymal transition gene signature. Moreover, in vitro studies revealed that CD73 and extracellular adenosine enhance ovarian tumor cell growth as well as expression of antiapoptotic BCL-2 family members. Finally, in vivo coinjection of ID8 mouse ovarian tumor cells with mouse embryonic fibroblasts showed that CD73 expression in fibroblasts promotes tumor immune escape and thereby tumor growth. In conclusion, our study highlights a role for CD73 as a prognostic marker of patient survival and also as a candidate therapeutic target in HGS ovarian cancers.Cancer Res; 75(21); 4494-503. Ó2015 AACR.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

CD73 Is Associated with Poor Prognosis in High-Grade Serous Ovarian Cancer

et al. 2015

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“…As previously mentioned, TGF-β is one of the most powerful inducers of EMT; for example, in a gallbladder carcinoma cell line it promotes a mesenchymal phenotype with a notorious increase in the expression of ectonucleotidase CD73, the enzyme that dephosphorylates AMP to adenosine, suggesting that the nucleoside could be fundamental in the EMT induction program activated by TGF-β in this cell line [93]. However, CD73 has been part of a polemic argument regarding its involvement in the cancerous process.…”

Section: Adora2amentioning

confidence: 70%

Nucleotides and nucleoside signaling in the regulation of the epithelium to mesenchymal transition (EMT)

Martinez-Ramirez

Dı́az-Muñoz

Butanda-Ochoa

et al. 2016

Purinergic Signalling

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The epithelium-mesenchymal transition (EMT) is an important process of cell plasticity, consisting in the loss of epithelial identity and the gain of mesenchymal characteristics through the coordinated activity of a highly regulated informational program. Although it was originally described in the embryonic development, an important body of information supports its role in pathology, mainly in cancerous and fibrotic processes. The purinergic system of inter-cellular communication, mainly based in ATP and adenosine acting throughout their specific receptors, has emerged as a potent regulator of the EMT in several pathological entities. In this context, cellular signaling associated to purines is opening the understanding of a new element in the complex regulatory network of this phenotypical differentiation process. In this review, we have summarized recent information about the role of ATP and adenosine in EMT, as a growing field with high therapeutic potential.Keywords P2 receptors . P1 receptors . Purinergic signaling . Cell migration . EMTThe purinergic system of intercellular communication General aspects The term purine (from: pure urine) was created more than 130 years ago by Emil Fischer after detailed analytical characterization of the uric acid molecule [1]. Purine molecular structure is the result of fusing pyrimidine and imidazole rings, and it exists as four N-H tautomeric forms [2]. Tautomerism of purine bases in DNA is one of the earliest reasons for mutations [3][4][5]. The interconversion of the different adenine or guanine tautomers produced mispairing with pyrimidines (which also show tautomeric forms) that may lead to changes in DNA sequence [6].Purine molecules appeared very early in the history of our planet, in the period known as Borganic evolution^, before the establishment of living systems. It has been postulated that purines could be formed by a eutectic (denoting a mixture of substances in fixed proportions that melts and freezes at a single temperature that is lower than the melting points of any of the separate constituents) concentration of HCN at extremely low temperature over a period of dozens of years [7]. Purine molecules, such as adenine and guanine, are components of the genetic material (DNA and RNA) of all living beings. Purine and pyrimidine tautomeric equilibria in nucleic acids was postulated to be significant in events such as DNA replication and repair as well as in the occurrence of point mutations [8].As nucleosides and nucleotides, purines play other highly strategic roles, acting as energy intermediates, allosteric regulators of key metabolic activities, redox molecules, and chemical messengers for signal transduction events. The two most important purines serving as extracellular ligands for paracrine and autocrine signaling are ATP and its dephosphorylated form, adenosine (ADO). ATP and ADO act as intracellular intermediate metabolites, and their presence in the

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“…According to the UCSC Genome Browser and Database of Genomic Variants [25,26], this duplicated region is located within the FCGBP gene. Characterized by the production of a large (encoded by a 17-kb mRNA) mucin-like protein that binds the Fc portion of IgG molecules, this gene has been reported as differentially expressed in gallbladder [45], prostate [46], thyroid [47], lung [48], colon [49], and ovarian cancer [50]. Present in serum, the protein can be found in higher levels in patients with autoimmune diseases [51].…”

Section: Discussionmentioning

confidence: 99%

Copy number variation analysis reveals additional variants contributing to endometriosis development

Mafra

Mazzotti

Pellegrino

et al. 2016

J Assist Reprod Genet

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Purpose Endometriosis is a gynecological disease influenced by multiple genetic and environmental factors. The aim of the current study was to use SNP-array technology to identify genomic aberrations that may possibly contribute to the development of endometriosis. Methods We performed an SNP-array genotyping of pooled DNA samples from both patients (n = 100) and controls (n = 50). Copy number variation (CNV) calling and association analyses were performed using PennCNV software. MLPA and TaqMan Copy-Number assays were used for validation of CNVs discovered. Results We detected 49 CNV loci that were present in patients with endometriosis and absent in the control group. After validation procedures, we confirmed six CNV loci in the subtelomeric regions, including 1p36. 33, 16p13.3, 19p13.3, and 20p13, representing gains, while 17q25.3 and 20q13.33 showed losses. Among the intrachromosomal regions, our results revealed duplication at 19q13.1 within the FCGBP gene (p = 0.007). Conclusions We identified CNVs previously associated with endometriosis, together with six suggestive novel loci possibly involved in this disease. The intergenic locus on chromosome 19q13.1 shows strong association with endometriosis and is under further functional investigation.

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NT5E and FcGBP as key regulators of TGF-1-induced epithelial–mesenchymal transition (EMT) are associated with tumor progression and survival of patients with gallbladder cancer

Cited by 121 publications

References 24 publications

CD73 Is Associated with Poor Prognosis in High-Grade Serous Ovarian Cancer

CD73 Is Associated with Poor Prognosis in High-Grade Serous Ovarian Cancer

Nucleotides and nucleoside signaling in the regulation of the epithelium to mesenchymal transition (EMT)

Copy number variation analysis reveals additional variants contributing to endometriosis development

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