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Keywords {🔍}

snai, runx, expression, cancer, bca, cells, pubmed, figure, article, metastasis, google, scholar, breast, tumors, cas, emt, bone, genes, high, erα, transcription, cell, signaling, analysis, mcfrxdox, dox, estrogen, factor, gene, gse, central, data, role, expressing, file, esr, levels, rtqpcr, invasiveness, correlation, invasion, association, stimulated, wnt, negative, lung, additional, low, activity, boneseeking,

Topics {✒️}

β-catenin/lef/tcf complexes [35] wnt/β-catenin pathway-related genes tgf-beta induced transdifferentiation c4-2b/rx2dox pca cells log2-transformed signal intensities cleidocranial dysplasia syndrome organ-specific metastasis-free survival article download pdf site-specific metastasis-free survival full size image dox-induced shrna-mediated silencing mcf7/rx2dox culture system caat-enhancer binding protein runx-binding motifs upstream lineage-specific transcription factor slug regulates e-cadherin anti-tgf-β type log2-transformed significance values cyclin-dependent kinase inhibitor metastasis-free survival time src-dependent survival signals transcriptionally repress e-cadherin affymetrix chips hg-u133a zinc-finger transcription factors genome-wide expression profiling genome-wide runx2 occupancy mcf7/rx2dox cells transduced t47d/shrx2dox bca cells mcf7/rx2dox bca cells taking gene-expression profiling epithelial marker e-cadherin epithelial-mesenchymal transition mouse monoclonal anti-snai2 constructing kaplan-meier curves runx2-induced emt characteristics rna interference abolished runx2 chip-seq analysis bone metastasis-free survival snail1-twist1 conspiracy mcf7/rx2dox cells treated e2-resistant signaling pathways phenol red-free dmem esr1/erα gene expressions bone-seeking bca cells favorable prognostic marker mcf7/rx2dox cell invasiveness bioinformatics service program respective kaplan-meier curves transcriptional inhibitor belonging er-negative tumors contributes

Questions {❓}

• Peinado H, Olmeda D, Cano A: Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype?
• Sotiriou C, Piccart MJ: Taking gene-expression profiling to the clinic: when will molecular signatures become relevant to patient care?

Schema {🗺️}

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         headline:Regulation of breast cancer metastasis by Runx2 and estrogen signaling: the role of SNAI2
         description:In contrast to its role in breast cancer (BCa) initiation, estrogen signaling has a protective effect in later stages, where estrogen receptor (ER)α loss associates with aggressive metastatic disease. We asked whether the beneficial effect of estrogen signaling in late-stage BCa is attributable to the recently reported estrogen-mediated antagonism of the pro-metastatic transcription factor Runx2. MCF7/Rx2dox breast cancer cells were engineered with a lentivirus expressing Runx2 in response to doxycycline (dox). Cells treated with dox and/or estradiol (E2) were subjected to genome-wide expression profiling, RT-qPCR analysis of specific genes, and Matrigel™ invasion assays. Knockdown of genes of interest was performed using lentiviruses expressing appropriate shRNAs, either constitutively or in response to dox. Gene expression in BCa tumors was investigated using a cohort of 557 patients compiled from publicly available datasets. Association of gene expression with clinical metastasis was assessed by dichotomizing patients into those expressing genes of interest at either high or low levels, and comparing the respective Kaplan-Meier curves of metastasis-free survival. Runx2 induced epithelial-mesenchymal transition (EMT) evidenced by acquisition of a fibroblastic morphology, decreased expression of E-cadherin, increased expression of vimentin and invasiveness. Runx2 stimulated SNAI2 expression in a WNT- and transforming growth factor (TGF)β-dependent manner, and knockdown of SNAI2 abrogated the pro-metastatic activities of Runx2. E2 antagonized the pro-metastatic activities of Runx2, including SNAI2 upregulation. In primary BCa tumors, Runx2 activity, SNAI2 expression, and metastasis were positively correlated, and SNAI2 expression was negatively correlated with ERα. However, the negative correlation between SNAI2 and ERα in bone-seeking BCa cells was weaker than the respective negative correlation in tumors seeking lung. Furthermore, the absence of ERα in primary tumors was associated with lung- and brain- but not with bone metastasis, and tumor biopsies from bone metastatic sites displayed the unusual combination of high Runx2/SNAI2 and high ERα expression. E2 antagonizes Runx2-induced EMT and invasiveness of BCa cells, partly through attenuating expression of SNAI2, a Runx2 target required for mediating its pro-metastatic property. That ERα loss promotes non-osseous metastasis by unleashing Runx2/SNAI2 is supported by the negative correlation observed in corresponding tumors. Unknown mechanisms in bone-seeking BCa allow high Runx2/SNAI2 expression despite high ERα level
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            Estrogen Signaling
            Cleidocranial Dysplasia
            SNAI2 Expression
            Runx2 Target Gene
            Cancer Research
            Oncology
            Surgical Oncology
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         Estrogen Signaling
         Cleidocranial Dysplasia
         SNAI2 Expression
         Runx2 Target Gene
         Cancer Research
         Oncology
         Surgical Oncology
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            name:Keck School of Medicine of the University of Southern California
            address:
               name:Will Rogers Institute Pulmonary Research Center, Keck School of Medicine of the University of Southern California, Los Angeles, USA
               type:PostalAddress
            type:Organization
      name:Baruch Frenkel
      affiliation:
            name:Keck School of Medicine of the University of Southern California
            address:
               name:Department of Biochemistry & Molecular Biology, Keck School of Medicine of the University of Southern California, Los Angeles, USA
               type:PostalAddress
            type:Organization
            name:Keck School of Medicine of the University of Southern California
            address:
               name:Institute for Genetic Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, USA
               type:PostalAddress
            type:Organization
            name:Keck School of Medicine of the University of Southern California
            address:
               name:Department of Orthopedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Biochemistry & Molecular Biology, Keck School of Medicine of the University of Southern California, Los Angeles, USA
      name:Institute for Genetic Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, USA
      name:Institute for Genetic Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, USA
      name:Department of Orthopedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, USA
      name:Department of Biochemistry & Molecular Biology, Keck School of Medicine of the University of Southern California, Los Angeles, USA
      name:Institute for Genetic Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, USA
      name:Bioinformatics Service Program, Norris Medical Library, University of Southern California, Los Angeles, USA
      name:Department of Biochemistry & Molecular Biology, Keck School of Medicine of the University of Southern California, Los Angeles, USA
      name:Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, USA
      name:Department of Biochemistry & Molecular Biology, Keck School of Medicine of the University of Southern California, Los Angeles, USA
      name:Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, USA
      name:Will Rogers Institute Pulmonary Research Center, Keck School of Medicine of the University of Southern California, Los Angeles, USA
      name:Department of Biochemistry & Molecular Biology, Keck School of Medicine of the University of Southern California, Los Angeles, USA
      name:Institute for Genetic Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, USA
      name:Department of Orthopedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, USA

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