Similar Datasets
Project description:Tumor heterogeneity, the presence of multiple distinct subpopulations of cancer cells between patients or among the same tumors, poses a major challenge to current targeted therapies. The way these different subpopulations interact among themselves and the stromal niche environment, and how such interactions affect cancer stem cell behavior has remained largely unknown. Here, it is shown that an FGF-BMP7-INHBA signaling positive feedback loop integrates interactions among different cell populations, including mammary gland stem cells, luminal epithelial and stromal fibroblast niche components not only in organ regeneration but also, with certain modifications, in cancer progression. The reciprocal dependence of basal stem cells and luminal epithelium is based on basal-derived BMP7 and luminal-derived INHBA, which promote their respective expansion, and is regulated by stromal-epithelial FGF signaling. Targeting this interaction loop, for example, by reducing the function of one or more of its components, inhibits organ regeneration and breast cancer progression. The results have profound implications for overcoming drug resistance because of tumor heterogeneity in future targeted therapies.
| S-EPMC11234407 | biostudies-literature
Project description:Targeting cancer heterogeneity by breaking a stem cell and epithelial niche interaction loop
| PRJNA933086 | ENA
Project description:The aim of this work was to elucidate the role of the transcription factor CXXC5 in glioblastoma and study its involvement in the regulation of TGFβ and BMP target genes in this context. To this end we used the patient derived glioblastoma stem cells U3034MG that were either transfected with siRNA targeting CXXC5 or with a non-targeting pool (as control) followed by stimulation with either 5ng/ml TGFβ or 30ng/ml BMP7 for 24 h. Then we analysed how silencing CXXC5 affects the expression of TGFβ and/or BMP7 target genes using Ion torrent AmpliseqTM.
2021-05-01 | E-MTAB-9813 | biostudies-arrayexpress
Project description:Basal-like and luminal breast tumors have distinct clinical behavior and molecular profiles, yet the underlying mechanisms are poorly defined. To interrogate processes that determine these distinct phenotypes and their inheritance pattern, we generated somatic cell fusions and performed integrated genetic and epigenetic (DNA methylation and chromatin) profiling. We found that the basal-like trait is generally dominant and it is largely defined by epigenetic repression of luminal transcription factors. Definition of super-enhancers highlighted a core program common in luminal cells but high degree of heterogeneity in basal-like breast cancers that correlates with clinical outcome. We also found that protein extracts of basal-like cells is sufficient to induce luminal-to-basal phenotypic switch implying a trigger of basal-like autoregulatory circuits. We determined that KDM6A might be required for luminal-basal fusions, and identified EN1, TBX18, and TCF4 as candidate transcriptional regulators of luminal-to-basal switch. Our findings highlight the remarkable epigenetic plasticity of breast cancer cells. Digital gene expression profiles of basal-like, luminal and their heterofusion cells were generated by deep sequencing, using Helicos HeliScope.
2015-06-10 | E-GEOD-38790 | biostudies-arrayexpress
Project description:Basal-like and luminal breast tumors have distinct clinical behavior and molecular profiles, yet the underlying mechanisms are poorly defined. To interrogate processes that determine these distinct phenotypes and their inheritance pattern, we generated somatic cell fusions and performed integrated genetic and epigenetic (DNA methylation and chromatin) profiling. We found that the basal-like trait is generally dominant and it is largely defined by epigenetic repression of luminal transcription factors. Definition of super-enhancers highlighted a core program common in luminal cells but high degree of heterogeneity in basal-like breast cancers that correlates with clinical outcome. We also found that protein extracts of basal-like cells is sufficient to induce luminal-to-basal phenotypic switch implying a trigger of basal-like autoregulatory circuits. We determined that KDM6A might be required for luminal-basal fusions, and identified EN1, TBX18, and TCF4 as candidate transcriptional regulators of luminal-to-basal switch. Our findings highlight the remarkable epigenetic plasticity of breast cancer cells. Bisulphite converted DNA from the 9 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip.
2015-06-10 | E-GEOD-38791 | biostudies-arrayexpress
Project description:Basal-like and luminal breast tumors have distinct clinical behavior and molecular profiles, yet the underlying mechanisms are poorly defined. To interrogate processes that determine these distinct phenotypes and their inheritance pattern, we generated somatic cell fusions and performed integrated genetic and epigenetic (DNA methylation and chromatin) profiling. We found that the basal-like trait is generally dominant and it is largely defined by epigenetic repression of luminal transcription factors. Definition of super-enhancers highlighted a core program common in luminal cells but high degree of heterogeneity in basal-like breast cancers that correlates with clinical outcome. We also found that protein extracts of basal-like cells is sufficient to induce luminal-to-basal phenotypic switch implying a trigger of basal-like autoregulatory circuits. We determined that KDM6A might be required for luminal-basal fusions, and identified EN1, TBX18, and TCF4 as candidate transcriptional regulators of luminal-to-basal switch. Our findings highlight the remarkable epigenetic plasticity of breast cancer cells. Bisulphite converted DNA from 20 breast cancer cell lines were hybridized to the Illumina Infinium HumanMethylation450 BeadChip.
2015-06-10 | E-GEOD-67619 | biostudies-arrayexpress
Project description:Recent studies suggest the presence of both âclassically activatedâ M1 and âalternatively activatedâ M2 macrophages in human atherosclerotic tissue, yet due to the lack of validated markers the reported localization patterns of these macrophage phenotypes within plaques are ambiguous. In the present study, we searched for markers that indisputably can identify differentiated M1 and M2 macrophages independently of stimuli that affect the activation status of the two subpopulations. We used these validated markers to assess the presence of M1 and M2 macrophages in different zones of human carotid artery atherosclerotic plaques obtained from 12 patients. Using microarray and qPCR technology we show that the frequently used macrophage subpopulation markers MCP-1 and CD206 do not discriminate between M1 and M2 macrophages. However, we confirm the subtype specificity of the classical M2 marker CD163 and we report that the genes INHBA and DSP (both M1) and SEPP1 and MARCKS (both M2) are highly suitable for macrophage phenotyping. mRNA expression of the pan-macrophage marker CD68 in the shoulder zones of the plaques and in adjacent tissue segments correlated positively with mRNA expression levels of SEPP1, MARCKS and CD163 (r=0.86, 0.94 and 0.96, and r= 0.86, 0.98 and 0.69, respectively) but not with the expression of the M1 markers DSP and INHBA. In contrast, mRNA expression of CD68 in the core of the plaques correlated positively with expression of DSP and INHBA (r=0.73 and 0.49) but not with SEPP1, MARCKS and CD163. These findings suggest that M1 macrophages predominate in the core of human carotid atherosclerotic plaques while M2 macrophages prevail at the periphery of the plaque. Keywords: Expression profiling by array Monocytes from healthy volunteers were differentiated into M1 and M2 macrophages by incubation with granulocyte-macrophage colony-stimulating factor (GM-CSF) or macrophage colony-stimulating factor (M-CSF), respectively. After 5 days cells were exposed to oxidized LDL. Total RNA was isolated and subjected to gene expression profiling.
2016-06-01 | E-GEOD-22543 | biostudies-arrayexpress
Project description:Basal-like and luminal breast tumors have distinct clinical behavior and molecular profiles, yet the underlying mechanisms are poorly defined. To interrogate processes that determine these distinct phenotypes and their inheritance pattern, we generated somatic cell fusions and performed integrated genetic and epigenetic (DNA methylation and chromatin) profiling. We found that the basal-like trait is generally dominant and it is largely defined by epigenetic repression of luminal transcription factors. Definition of super-enhancers highlighted a core program common in luminal cells but high degree of heterogeneity in basal-like breast cancers that correlates with clinical outcome. We also found that protein extracts of basal-like cells is sufficient to induce luminal-to-basal phenotypic switch implying a trigger of basal-like autoregulatory circuits. We determined that KDM6A might be required for luminal-basal fusions, and identified EN1, TBX18, and TCF4 as candidate transcriptional regulators of luminal-to-basal switch. Our findings highlight the remarkable epigenetic plasticity of breast cancer cells. We investigated the potential contribution of genetic factors to defining cell type-specific gene expression patterns by analyzing allelic inheritance based on Affymetrix SNP6.0 array hybridization of DNA from parental and fusion cells
2015-06-10 | E-GEOD-39412 | biostudies-arrayexpress
Project description:Basal-like and luminal breast tumors have distinct clinical behavior and molecular profiles, yet the underlying mechanisms are poorly defined. To interrogate processes that determine these distinct phenotypes and their inheritance pattern, we generated somatic cell fusions and performed integrated genetic and epigenetic (DNA methylation and chromatin) profiling. We found that the basal-like trait is generally dominant and it is largely defined by epigenetic repression of luminal transcription factors. Definition of super-enhancers highlighted a core program common in luminal cells but high degree of heterogeneity in basal-like breast cancers that correlates with clinical outcome. We also found that protein extracts of basal-like cells is sufficient to induce luminal-to-basal phenotypic switch implying a trigger of basal-like autoregulatory circuits. We determined that KDM6A might be required for luminal-basal fusions, and identified EN1, TBX18, and TCF4 as candidate transcriptional regulators of luminal-to-basal switch. Our findings highlight the remarkable epigenetic plasticity of breast cancer cells. RNA-Seq in breast cancer cell-lines
2015-06-10 | E-GEOD-69114 | biostudies-arrayexpress
Project description:Basal-like and luminal breast tumors have distinct clinical behavior and molecular profiles, yet the underlying mechanisms are poorly defined. To interrogate processes that determine these distinct phenotypes and their inheritance pattern, we generated somatic cell fusions and performed integrated genetic and epigenetic (DNA methylation and chromatin) profiling. We found that the basal-like trait is generally dominant and it is largely defined by epigenetic repression of luminal transcription factors. Definition of super-enhancers highlighted a core program common in luminal cells but high degree of heterogeneity in basal-like breast cancers that correlates with clinical outcome. We also found that protein extracts of basal-like cells is sufficient to induce luminal-to-basal phenotypic switch implying a trigger of basal-like autoregulatory circuits. We determined that KDM6A might be required for luminal-basal fusions, and identified EN1, TBX18, and TCF4 as candidate transcriptional regulators of luminal-to-basal switch. Our findings highlight the remarkable epigenetic plasticity of breast cancer cells. Examination of histone H3K27me3 modifications in various breast cancer cell lines.
2015-06-10 | E-GEOD-38789 | biostudies-arrayexpress