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We are analyzing https://link.springer.com/article/10.1186/1471-2407-14-734.

Title:
The basal epithelial marker P-cadherin associates with breast cancer cell populations harboring a glycolytic and acid-resistant phenotype | BMC Cancer
Description:
Background Cancer stem cells are hypoxia-resistant and present a preponderant glycolytic metabolism. These characteristics are also found in basal-like breast carcinomas (BLBC), which show increased expression of cancer stem cell markers. Recently, we demonstrated that P-cadherin, a biomarker of BLBC and a poor prognostic factor in this disease, mediates stem-like properties and resistance to radiation therapy. Thus, the aim of the present study was to evaluate if P-cadherin expression was associated to breast cancer cell populations with an adapted phenotype to hypoxia. Methods Immunohistochemistry was performed to address the expression of P-cadherin, hypoxic, glycolytic and acid-resistance biomarkers in primary human breast carcinomas. In vitro studies were performed using basal-like breast cancer cell lines. qRT-PCR, FACS analysis, western blotting and confocal microscopy were used to assess the expression of P-cadherin after HIF-1α stabilization, achieved by CoCl2 treatment. siRNA-mediated knockdown was used to silence the expression of several targets and qRT-PCR was employed to evaluate the effects of P-cadherin on HIF-1α signaling. P-cadherin high and low breast cancer cell populations were sorted by FACS and levels of GLUT1 and CAIX were assessed by FACS and western blotting. Mammosphere forming efficiency was used to determine the stem cell activity after specific siRNA-mediated knockdown, further confirmed by western blotting. Results We demonstrated that P-cadherin overexpression was significantly associated with the expression of HIF-1α, GLUT1, CAIX, MCT1 and CD147 in human breast carcinomas. In vitro, we showed that HIF-1α stabilization was accompanied by increased membrane expression of P-cadherin and that P-cadherin silencing led to a decrease of the mRNA levels of GLUT1 and CAIX. We also found that the cell fractions harboring high levels of P-cadherin were the same exhibiting more GLUT1 and CAIX expression. Finally, we showed that P-cadherin silencing significantly decreases the mammosphere forming efficiency in the same range as the silencing of HIF-1α, CAIX or GLUT1, validating that all these markers are being expressed by the same breast cancer stem cell population. Conclusions Our results establish a link between aberrant P-cadherin expression and hypoxic, glycolytic and acid-resistant breast cancer cells, suggesting a possible role for this marker in cancer cell metabolism.
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🌠 Phenomenal Traffic: 5M - 10M visitors per month


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Keywords {🔍}

cancer, breast, expression, pcadherin, cells, cell, pubmed, glut, caix, article, hifα, google, scholar, cas, stem, mct, cdh, figure, hypoxia, usa, carcinomas, tumor, basallike, central, analysis, phenotype, levels, membrane, significant, glycolytic, paredes, schmitt, markers, silencing, association, metabolism, increased, primary, human, mrna, res, data, metabolic, file, observed, demonstrated, properties, lines, molecular, invasive,

Topics {✒}

scientific project ptdc/sau-gmg/120049/2010-fcomp-01-0124-feder-021209 project ptdc/sau-gmg/120049/2010 pre-publication history alexa-594-conjugated secondary igg p-cadherin-deficient mice hrp-conjugated anti-mouse induced-pluripotent stem cells cĂ©line pinheiro deionized phosphate-buffered saline apc-conjugated p-cadherin endogenous cadherin/catenin complex brca1-related breast cancer peri-necrotic tumor areas 18 f-fdg pet scan open access license gtpase-mediated signal transduction tumor-initiating cell activity ÎČ-actin [clone i-19 carbonic anhydrase ix fernando schmitt & joana paredes brca1-mutated breast carcinomas caix expression profiles article download pdf acid-resistant phenotype markers triple-negative breast cancer gene-specific idt probes inducing sirna-mediated knockdown gene expression profile aberrant p-cadherin expression quantitative-real-time-pcr real-time quantitative pcr membrane p-cadherin expression sirna cdh3 + hif-1α + glut1 + caix primary anti-human antibodies markers including hif-1α divino espĂ­rito santo hypoxia-induced epigenetic regulation full size image z-stack measurements revealed specific sirna-mediated knockdown ptdc/sau-fcf/104347/2008 e-cadherin cellular context lowest p-cadherin expression p-cadherin silencing led ductal mammary branching cell subpopulation expressing poor prognostic factor cdh3/p-cadherin promoter [36] author information authors results p-cadherin overexpression

Questions {❓}

  • Paredes J, Milanezi F, Reis-Filho JS, Leitao D, Athanazio D, Schmitt F: Aberrant P-cadherin expression: is it associated with estrogen-independent growth in breast cancer?

Schema {đŸ—ș}

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         description:Cancer stem cells are hypoxia-resistant and present a preponderant glycolytic metabolism. These characteristics are also found in basal-like breast carcinomas (BLBC), which show increased expression of cancer stem cell markers. Recently, we demonstrated that P-cadherin, a biomarker of BLBC and a poor prognostic factor in this disease, mediates stem-like properties and resistance to radiation therapy. Thus, the aim of the present study was to evaluate if P-cadherin expression was associated to breast cancer cell populations with an adapted phenotype to hypoxia. Immunohistochemistry was performed to address the expression of P-cadherin, hypoxic, glycolytic and acid-resistance biomarkers in primary human breast carcinomas. In vitro studies were performed using basal-like breast cancer cell lines. qRT-PCR, FACS analysis, western blotting and confocal microscopy were used to assess the expression of P-cadherin after HIF-1α stabilization, achieved by CoCl2 treatment. siRNA-mediated knockdown was used to silence the expression of several targets and qRT-PCR was employed to evaluate the effects of P-cadherin on HIF-1α signaling. P-cadherin high and low breast cancer cell populations were sorted by FACS and levels of GLUT1 and CAIX were assessed by FACS and western blotting. Mammosphere forming efficiency was used to determine the stem cell activity after specific siRNA-mediated knockdown, further confirmed by western blotting. We demonstrated that P-cadherin overexpression was significantly associated with the expression of HIF-1α, GLUT1, CAIX, MCT1 and CD147 in human breast carcinomas. In vitro, we showed that HIF-1α stabilization was accompanied by increased membrane expression of P-cadherin and that P-cadherin silencing led to a decrease of the mRNA levels of GLUT1 and CAIX. We also found that the cell fractions harboring high levels of P-cadherin were the same exhibiting more GLUT1 and CAIX expression. Finally, we showed that P-cadherin silencing significantly decreases the mammosphere forming efficiency in the same range as the silencing of HIF-1α, CAIX or GLUT1, validating that all these markers are being expressed by the same breast cancer stem cell population. Our results establish a link between aberrant P-cadherin expression and hypoxic, glycolytic and acid-resistant breast cancer cells, suggesting a possible role for this marker in cancer cell metabolism.
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      headline:The basal epithelial marker P-cadherin associates with breast cancer cell populations harboring a glycolytic and acid-resistant phenotype
      description:Cancer stem cells are hypoxia-resistant and present a preponderant glycolytic metabolism. These characteristics are also found in basal-like breast carcinomas (BLBC), which show increased expression of cancer stem cell markers. Recently, we demonstrated that P-cadherin, a biomarker of BLBC and a poor prognostic factor in this disease, mediates stem-like properties and resistance to radiation therapy. Thus, the aim of the present study was to evaluate if P-cadherin expression was associated to breast cancer cell populations with an adapted phenotype to hypoxia. Immunohistochemistry was performed to address the expression of P-cadherin, hypoxic, glycolytic and acid-resistance biomarkers in primary human breast carcinomas. In vitro studies were performed using basal-like breast cancer cell lines. qRT-PCR, FACS analysis, western blotting and confocal microscopy were used to assess the expression of P-cadherin after HIF-1α stabilization, achieved by CoCl2 treatment. siRNA-mediated knockdown was used to silence the expression of several targets and qRT-PCR was employed to evaluate the effects of P-cadherin on HIF-1α signaling. P-cadherin high and low breast cancer cell populations were sorted by FACS and levels of GLUT1 and CAIX were assessed by FACS and western blotting. Mammosphere forming efficiency was used to determine the stem cell activity after specific siRNA-mediated knockdown, further confirmed by western blotting. We demonstrated that P-cadherin overexpression was significantly associated with the expression of HIF-1α, GLUT1, CAIX, MCT1 and CD147 in human breast carcinomas. In vitro, we showed that HIF-1α stabilization was accompanied by increased membrane expression of P-cadherin and that P-cadherin silencing led to a decrease of the mRNA levels of GLUT1 and CAIX. We also found that the cell fractions harboring high levels of P-cadherin were the same exhibiting more GLUT1 and CAIX expression. Finally, we showed that P-cadherin silencing significantly decreases the mammosphere forming efficiency in the same range as the silencing of HIF-1α, CAIX or GLUT1, validating that all these markers are being expressed by the same breast cancer stem cell population. Our results establish a link between aberrant P-cadherin expression and hypoxic, glycolytic and acid-resistant breast cancer cells, suggesting a possible role for this marker in cancer cell metabolism.
      datePublished:2014-10-01T00:00:00Z
      dateModified:2014-10-01T00:00:00Z
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      pageEnd:13
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      sameAs:https://doi.org/10.1186/1471-2407-14-734
      keywords:
         P-cadherin
         Breast cancer
         Hypoxia
         Cancer stem cells
         Cancer Research
         Oncology
         Surgical Oncology
         Health Promotion and Disease Prevention
         Biomedicine
         general
         Medicine/Public Health
      image:
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2F1471-2407-14-734/MediaObjects/12885_2014_Article_4912_Fig1_HTML.jpg
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      name:IPATIMUP- Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
      name:IPATIMUP- Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
      name:IPATIMUP- Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
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