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Title:
Transcription Factor Networks in Invasion-Promoting Breast Carcinoma-Associated Fibroblasts | Cancer Microenvironment
Description:
Carcinoma-associated fibroblasts (CAFs) contribute to both tumor growth and cancer progression. In this report, we applied an emerging transcription factor (TF) activity array to fibroblasts to capture the activity of the intracellular signaling network and to define a signature that distinguishes mammary CAFs from normal mammary fibroblasts. Normal fibroblasts that restrained cancer cell invasion developed into an invasion-promoting CAF phenotype through exposure to conditioned medium from MDA-MB-231 breast cancer cells. A myofibroblast-like CAF cell line expressing high levels of smooth muscle actin was compared to normal mammary fibroblasts before and after induction. Comparison of TF activity profiles for all three fibroblast types identified a TF activity signature common to CAFs which included activation of reporters for TFs ELK1, GATA1, retinoic acid receptor (RAR), serum response factor (SRF), and vitamin D receptor (VDR). Additionally, CAFs resembling myofibroblasts, relative to normal fibroblasts, had elevated activation corresponding to NF-kappaB, RUNX2, and YY1, and distinct activity patterns for several differentiation-related TF reporters. Induction of CAFs by exposure of normal fibroblasts to conditioned medium from MDA-MB-231 cells resulted in increased activation of reporters for HIF1, several STAT TFs, and proliferation-related TFs such as AP1. Myofibroblast-like CAFs and induced normal mammary fibroblasts promoted invasion of breast cancer cells by distinct mechanisms, consistent with their distinct patterns of TF activation. The TF activity profiles of CAF subtypes provide an overview of intracellular signaling associated with the induction of a pro-invasive stroma, and provide a mechanistic link between the microenvironmental stimuli and phenotypic response.
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article, pubmed, google, scholar, cancer, cas, breast, fibroblasts, cell, stromal, tumor, cells, expression, normal, van, microenvironment, biol, human, shea, activity, res, transcription, factor, mammary, fibroblast, factors, usa, carcinomaassociated, stroma, rijn, gene, chicago, northwestern, university, analysis, jeruss, cafs, invasion, induction, activation, access, molecular, invasive, sci, brown, heterogeneity, privacy, cookies, content, growth,
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nf-kappab-yy1-mir-29 regulatory circuitry nf-kappab-dependent manner month download article/chapter transcription factor networks stromal cell-derived factor-1 invasion-promoting caf phenotype invasion-promoting breast carcinoma orchestrate tumor-promoting inflammation mda-mb-231 cells resulted emerging transcription factor transcription factor activity fibroblast activation protein/seprase nf-kappab caveolin-1 predicts outcome tumor cell invasion article cancer microenvironment elevated sdf-1/cxcl12 secretion serum response factor full article pdf related subjects human breast carcinomas differentiation-related tf reporters smooth muscle actin worse clinical outcome tumour biol autocrine tgf-beta gene expression signature privacy choices/manage cookies retinoic acid receptor matrix metalloproteinase-1 proliferation-related tfs transcription factors gene expression programs stromal cell expression van de vijver fibroblast secreted factors martinez-outschoorn ue tumor stromal microenvironment invasive cancer growth invasive breast cancer human breast tumours modular cell biology cell type specificity tumor-stroma interactions receptor tyrosine kinases grant number pl1eb00854 invasive breast lesions cancer-stroma interactions tumor cells induce invasive breast carcinoma
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headline:Transcription Factor Networks in Invasion-Promoting Breast Carcinoma-Associated Fibroblasts
description:Carcinoma-associated fibroblasts (CAFs) contribute to both tumor growth and cancer progression. In this report, we applied an emerging transcription factor (TF) activity array to fibroblasts to capture the activity of the intracellular signaling network and to define a signature that distinguishes mammary CAFs from normal mammary fibroblasts. Normal fibroblasts that restrained cancer cell invasion developed into an invasion-promoting CAF phenotype through exposure to conditioned medium from MDA-MB-231 breast cancer cells. A myofibroblast-like CAF cell line expressing high levels of smooth muscle actin was compared to normal mammary fibroblasts before and after induction. Comparison of TF activity profiles for all three fibroblast types identified a TF activity signature common to CAFs which included activation of reporters for TFs ELK1, GATA1, retinoic acid receptor (RAR), serum response factor (SRF), and vitamin D receptor (VDR). Additionally, CAFs resembling myofibroblasts, relative to normal fibroblasts, had elevated activation corresponding to NF-kappaB, RUNX2, and YY1, and distinct activity patterns for several differentiation-related TF reporters. Induction of CAFs by exposure of normal fibroblasts to conditioned medium from MDA-MB-231 cells resulted in increased activation of reporters for HIF1, several STAT TFs, and proliferation-related TFs such as AP1. Myofibroblast-like CAFs and induced normal mammary fibroblasts promoted invasion of breast cancer cells by distinct mechanisms, consistent with their distinct patterns of TF activation. The TF activity profiles of CAF subtypes provide an overview of intracellular signaling associated with the induction of a pro-invasive stroma, and provide a mechanistic link between the microenvironmental stimuli and phenotypic response.
datePublished:2012-10-23T00:00:00Z
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Carcinoma-associated fibroblasts
Breast cancer
Transcription factors
Gene regulation
Induction
Cancer Research
Oncology
Immunology
Cell Biology
Biochemistry
general
Biomedicine
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description:Carcinoma-associated fibroblasts (CAFs) contribute to both tumor growth and cancer progression. In this report, we applied an emerging transcription factor (TF) activity array to fibroblasts to capture the activity of the intracellular signaling network and to define a signature that distinguishes mammary CAFs from normal mammary fibroblasts. Normal fibroblasts that restrained cancer cell invasion developed into an invasion-promoting CAF phenotype through exposure to conditioned medium from MDA-MB-231 breast cancer cells. A myofibroblast-like CAF cell line expressing high levels of smooth muscle actin was compared to normal mammary fibroblasts before and after induction. Comparison of TF activity profiles for all three fibroblast types identified a TF activity signature common to CAFs which included activation of reporters for TFs ELK1, GATA1, retinoic acid receptor (RAR), serum response factor (SRF), and vitamin D receptor (VDR). Additionally, CAFs resembling myofibroblasts, relative to normal fibroblasts, had elevated activation corresponding to NF-kappaB, RUNX2, and YY1, and distinct activity patterns for several differentiation-related TF reporters. Induction of CAFs by exposure of normal fibroblasts to conditioned medium from MDA-MB-231 cells resulted in increased activation of reporters for HIF1, several STAT TFs, and proliferation-related TFs such as AP1. Myofibroblast-like CAFs and induced normal mammary fibroblasts promoted invasion of breast cancer cells by distinct mechanisms, consistent with their distinct patterns of TF activation. The TF activity profiles of CAF subtypes provide an overview of intracellular signaling associated with the induction of a pro-invasive stroma, and provide a mechanistic link between the microenvironmental stimuli and phenotypic response.
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Transcription factors
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