scholarly journals Assessing the functional role of caspase-8 gene variants in breast cancer

2010 ◽  
Vol 12 (S1) ◽  
Author(s):  
SH Rigas ◽  
M Parry ◽  
MW Reed ◽  
N Camp ◽  
A Cox
Keyword(s):  
Breast Cancer ◽  
Functional Role ◽  
Caspase 8 ◽  
Gene Variants

Intestinal dysbiosis augments liver disease progression via NLRP3 in a murine model of primary sclerosing cholangitis

Gut ◽  
2019 ◽  
Vol 68 (8) ◽  
pp. 1477-1492 ◽  
Author(s):  
Lijun Liao ◽  
Kai Markus Schneider ◽  
Eric J C Galvez ◽  
Mick Frissen ◽  
Hanns-Ulrich Marschall ◽  
...  
Keyword(s):  
Immune Response ◽  
Liver Injury ◽  
Sclerosing Cholangitis ◽  
Functional Role ◽  
Innate Immune ◽  
Caspase 8 ◽  
Inflammasome Activation ◽  
Intestinal Dysbiosis ◽  
Nlrp3 Inflammasome Activation

ObjectiveThere is a striking association between human cholestatic liver disease (CLD) and inflammatory bowel disease. However, the functional implications for intestinal microbiota and inflammasome-mediated innate immune response in CLD remain elusive. Here we investigated the functional role of gut–liver crosstalk for CLD in the murine Mdr2 knockout (Mdr2−/−) model resembling human primary sclerosing cholangitis (PSC).DesignMale Mdr2−/−, Mdr2−/− crossed with hepatocyte-specific deletion of caspase-8 (Mdr2−/−/Casp8∆hepa) and wild-type (WT) control mice were housed for 8 or 52 weeks, respectively, to characterise the impact of Mdr2 deletion on liver and gut including bile acid and microbiota profiling. To block caspase activation, a pan-caspase inhibitor (IDN-7314) was administered. Finally, the functional role of Mdr2−/−-associated intestinal dysbiosis was studied by microbiota transfer experiments.ResultsMdr2−/− mice displayed an unfavourable intestinal microbiota signature and pronounced NLRP3 inflammasome activation within the gut–liver axis. Intestinal dysbiosis in Mdr2−/− mice prompted intestinal barrier dysfunction and increased bacterial translocation amplifying the hepatic NLRP3-mediated innate immune response. Transfer of Mdr2−/− microbiota into healthy WT control mice induced significant liver injury in recipient mice, highlighting the causal role of intestinal dysbiosis for disease progression. Strikingly, IDN-7314 dampened inflammasome activation, ameliorated liver injury, reversed serum bile acid profile and cholestasis-associated microbiota signature.ConclusionsMDR2-associated cholestasis triggers intestinal dysbiosis. In turn, translocation of endotoxin into the portal vein and subsequent NLRP3 inflammasome activation contribute to higher liver injury. This process does not essentially depend on caspase-8 in hepatocytes, but can be blocked by IDN-7314.

scholarly journals Prognostic and functional role of subtype-specific tumor-stroma interaction in breast cancer

2017 ◽  
Vol 11 (10) ◽  
pp. 1399-1412 ◽  
Author(s):  
Giuseppe Merlino ◽  
Patrizia Miodini ◽  
Maurizio Callari ◽  
Francesca D'Aiuto ◽  
Vera Cappelletti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Functional Role ◽  
Tumor Stroma ◽  
Specific Tumor

scholarly journals NCAM and attached polysialic acid affect behaviors of breast epithelial cells through differential signaling pathways

2020 ◽  
Author(s):  
Lin Cao ◽  
Xin Wang ◽  
Juhong Yang ◽  
Jia Guo ◽  
Xiang Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Adhesion ◽  
Epithelial Cells ◽  
Functional Role ◽  
Polysialic Acid ◽  
Breast Epithelial Cells ◽  
Differential Signaling ◽  
Breast Epithelial

Abstract Background Neural cell adhesion molecule (NCAM), a common mammalian cell surface glycoprotein, is the major substrate of polysialic acid (PSA). Polysialylated NCAM occurs in many types of cancer, but rarely in normal adult tissues. Epithelial-mesenchymal transition (EMT) is an important process contributing to tumor metastasis. The functional role of NCAM hypersialylation in EMT is unclear. Method Expression of NCAM and PSA-NCAM in breast cancer progression were evaluated by western blot (WB), immunohistochemistry, semi-quantitative PCR and immunoprecipitation (IP). Overexpression of NCAM-140 and STX were performed to assess the functional role of NCAM hypersialylation by liposome transfection. Then, the cell proliferation ability was investigated with MTT assay. Transwell and wound closure assay were conducted to evaluate cell migratory ability. Phagokinetic gold sol assay and cell adhesion assay were performed to assess cell motility ability and cell adhesion ability, respectively. Furthermore, WB and IP were used to reveal the activated signaling pathway. Results The present study indicates that NCAM and attached polysialic acid affect behaviors of breast epithelial cells through differential signaling pathways, based on the following observations: (i) NCAM and PSA-NCAM were aberrantly regulated in breast cancer cells; (ii) NCAM and PSA-NCAM expression were upregulated in normal breast epithelial cells undergoing EMT; (iii) NCAM overexpression induced EMT in breast epithelial cells; (iv) NCAM promoted cell proliferation and migration through activation of a β-catenin/slug signaling pathway; (v) modification of PSA attached to NCAM inhibited cell adhesion and promoted cell motility through activation of an EGFR/STAT3 pathway. Conclusion These observations help clarify the molecular mechanisms whereby PSA and its major substrate NCAM modulate cell behaviors, and the significance of increased PSA expression on NCAM during EMT and tumor development.

scholarly journals Breast cancer risk, nightwork, and circadian clock gene polymorphisms

2014 ◽  
Vol 21 (4) ◽  
pp. 629-638 ◽  
Author(s):  
Thérèse Truong ◽  
Benoît Liquet ◽  
Florence Menegaux ◽  
Sabine Plancoulaine ◽  
Pierre Laurent-Puig ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Circadian Clock ◽  
Postmenopausal Women ◽  
Gene Polymorphisms ◽  
Clock Gene ◽  
Gene Variants ◽  
Circadian Clock Gene

Night shift work has been associated with an increased risk of breast cancer pointing to a role of circadian disruption. We investigated the role of circadian clock gene polymorphisms and their interaction with nightwork in breast cancer risk in a population-based case–control study in France including 1126 breast cancer cases and 1174 controls. We estimated breast cancer risk associated with each of the 577 single nucleotide polymorphisms (SNPs) in 23 circadian clock genes. We also used a gene- and pathway-based approach to investigate the overall effect on breast cancer of circadian clock gene variants that might not be detected in analyses based on individual SNPs. Interactions with nightwork were tested at the SNP, gene, and pathway levels. We found that two SNPs inRORA(rs1482057 and rs12914272) were associated with breast cancer in the whole sample and among postmenopausal women. In this subpopulation, we also reported an association with rs11932595 inCLOCK, and withCLOCK,RORA, andNPAS2in the analyses at the gene level. Breast cancer risk in postmenopausal women was also associated with overall genetic variation in the circadian gene pathway (P=0.04), but this association was not detected in premenopausal women. There was some evidence of an interaction betweenPER1and nightwork in breast cancer in the whole sample (P=0.024), although the effect was not statistically significant after correcting for multiple testing (P=0.452). Our results support the hypothesis that circadian clock gene variants modulate breast cancer risk.

scholarly journals Functional role of miR-10b in tamoxifen resistance of ER-positive breast cancer cells through down-regulation of HDAC4

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Aamir Ahmad ◽  
Kevin R. Ginnebaugh ◽  
Shuping Yin ◽  
Aliccia Bollig-Fischer ◽  
Kaladhar B. Reddy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Functional Role ◽  
Breast Cancer Cells ◽  
Tamoxifen Resistance ◽  
Down Regulation ◽  
Er Positive ◽  
Positive Breast Cancer

scholarly journals The Expression and Functional Role of Syndecan 4 in Breast Cancer

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Maria Elisabeth Lendorf ◽  
John R Couchman ◽  
Ulla M Wewer ◽  
Hinke A.B. Multhaupt
Keyword(s):  
Breast Cancer ◽  
Functional Role

scholarly journals NCAM and attached polysialic acid affect behaviors of breast epithelial cells through differential signaling pathways

2020 ◽  
Author(s):  
Lin Cao ◽  
Xin Wang ◽  
Juhong Yang ◽  
Jia Guo ◽  
Xiang Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Adhesion ◽  
Epithelial Cells ◽  
Signaling Pathway ◽  
Functional Role ◽  
Polysialic Acid ◽  
Breast Epithelial Cells ◽  
Differential Signaling ◽  
Breast Epithelial

Abstract Background Neural cell adhesion molecule (NCAM), a common mammalian cell surface glycoprotein, is the major substrate of polysialic acid (polySia). Polysialylated NCAM occurs in many types of cancer, but rarely in normal adult tissues. Epithelial-mesenchymal transition (EMT) is an important process contributing to tumor metastasis. The functional role of NCAM hypersialylation in EMT is unclear. Method Expression of NCAM and polysialylated NCAM in breast cancer progression were evaluated by western blot (WB), immunohistochemistry, semi-quantitative PCR and immunoprecipitation (IP). Overexpression of NCAM-140 and ST8SiaII were performed to assess the functional role of NCAM hypersialylation by liposome transfection. Cell proliferation ability was investigated with MTT assay. Transwell and wound closure assay were conducted to evaluate cell migratory ability. Phagokinetic gold sol assay and cell adhesion assay were performed to assess cell motility ability and cell adhesion ability, respectively. Furthermore, WB and IP were used to reveal the activated signaling pathway. Results The present study indicates that NCAM and attached polysialic acid affect behaviors of breast epithelial cells through differential signaling pathways, based on the following observations: (i) NCAM and polysialylated NCAM were aberrantly regulated in breast cancer cells; (ii) NCAM and polysialylated NCAM expression were upregulated in normal breast epithelial cells undergoing EMT; (iii) NCAM overexpression induced EMT in breast epithelial cells; (iv) NCAM promoted cell proliferation and migration through activation of a β-catenin/slug signaling pathway; (v) modification of polySia attached to NCAM inhibited cell adhesion and promoted cell motility through activation of an EGFR/STAT3 pathway. Conclusion This study demonstrates that NCAM and polysialylated NCAM facilitate different signaling pathway and affect different cell behaviors. Switching between the NCAM-mediated pathways appeared to depend on polySia decoration.

scholarly journals Inherited thrombophilic risk factors in Serbian breast cancer patients

Genetika ◽  
2019 ◽  
Vol 51 (2) ◽  
pp. 463-472
Author(s):  
Iva Pruner ◽  
Branko Tomic ◽  
Marija Dragojevic ◽  
Maja Gvozdenov ◽  
Mirjana Kovac ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cancer Patients ◽  
Cancer Susceptibility ◽  
Mthfr C677t ◽  
Control Group ◽  
Gene Variants ◽  
Breast Cancer Patients ◽  
Significant Difference

Breast cancer is the leading cause of cancer-related death among women. An increased burden of thrombotic events among breast cancer patients, leading to higher mortality and morbidity rates, is well established. There are a number of genetic risk factors associated with thrombosis, but their contribution to thrombotic tendencies in patients with cancer is not completely elucidated. We aimed to investigate possible role of FV Leiden, FII G20210A, MTHFR C677T and PAI-1 4G/5G gene variants in etiopathology of breast cancer and accompanying thrombosis in cohort of Serbian patients. Our study included 316 subject divided in three groups: breast cancer patients with (97) or without (99) accompanying thrombosis and healthy control group (120). According to our results, the prevalence for all four prothrombotic gene variants were similar in cancer patients with and without thrombosis and no statistically significant difference was observed between these groups. We detected lower frequency of MTHFR 677TT genotype in breast cancer patients when compared to control group (P=0.014; OR=0.145 (95%CI 0.031-0.679)), indicated that MTHFR C677T homozygosity could play a protective role in breast cancer susceptibility. Our study noted the lack of association between common prothrombotic gene variants and increased prothrombotic risk in Serbian breast cancer patients. Also, our results point out possible role of MTHFR 677TT genotype in etiology of breast cancer, but further studies on larger cohort of patients are needed.

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