Characterization of MCSP+ melanoma DCC and MelDCC lines
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PROVIDER: EGAS00001006702 | EGA |
REPOSITORIES: EGA
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Project description:Breast cancer is the second most common cancer globally. Most deaths from breast cancer are due to metastatic disease which often follows long periods of clinical dormancy. Understanding the mechanisms that disrupt the quiescence of dormant disseminated cancer cells (DCC) is crucial for addressing metastatic progression. Infection with respiratory viruses (e.g. influenza or SARS-CoV-2) is common and triggers an inflammatory response locally and systemically. Here we show that influenza virus infection leads to loss of the pro-dormancy mesenchymal phenotype in breast DCC in the lung, causing DCC proliferation within days of infection, and a greater than 100-fold expansion of carcinoma cells into metastatic lesions within two weeks. Such DCC phenotypic change and expansion is interleukin-6 (IL-6)-dependent. We further show that CD4 T cells are required for the maintenance of pulmonary metastatic burden post-influenza virus infection, in part through attenuation of CD8 cell responses in the lungs. Single-cell RNA-seq analyses reveal DCC-dependent impairment of T-cell activation in the lungs of infected mice. SARS-CoV-2 infected mice also showed increased breast DCC expansion in lungs post-infection. Expanding our findings to human observational data, we observed that cancer survivors contracting a SARS-CoV-2 infection have substantially increased risks of lung metastatic progression and cancer related death compared to cancer survivors who did not. These discoveries underscore the significant impact of respiratory viral infections on the resurgence of metastatic cancer, offering novel insights into the interconnection between infectious diseases and cancer metastasis.
2025-05-27 | GSE264175 | GEO
Project description:Breast cancer is the second most common cancer globally, with most deaths caused by metastatic disease, often following long periods of clinical dormancy1. Understanding the mechanisms that disrupt the quiescence of dormant disseminated cancer cells (DCC) is crucial for addressing metastatic progression. Respiratory viruses infections such as influenza or SARS-CoV-2, trigger both local and systemic inflammation2,3. Here we demonstrate that influenza virus and SARS-CoV-2 infections lead to loss of the pro-dormancy phenotype in breast DCC in the lung, causing DCC proliferation within days of infection, and a massive expansion of carcinoma cells into metastatic lesions within two weeks. This phenotypic transition and expansion are interleukin-6 (IL-6)-dependent. We show that CD4+ T cells sustain pulmonary metastatic burden post-influenza infection by suppressing CD8+ T cell responses. Additionally, DCCs impair lung T-cell activation and tumor cell killing in infected mice. Critically, these experimental findings align with human observational data. Analyses of cancer survivors from the UK Biobank and Flatiron Health databases reveal that SARS-CoV-2 infection substantially increases the risk of lung metastasis and cancer-related mortality compared to uninfected cancer survivors. Notably, the heightened risk is most pronounced in the months following infection, paralleling experimental observations of accelerated DCC proliferation and metastatic progression shortly after viral infection. These discoveries underscore the significant impact of respiratory viral infections on metastatic cancer resurgence, offering novel insights into the interconnection between infectious diseases and cancer metastasis.
2025-05-27 | GSE282438 | GEO
Project description:In many species, a dosage compensation complex (DCC) is targeted to X chromosomes of one sex to equalize levels of X gene products between males (1X) and females (2X). Here we identify cis-acting regulatory elements that target the C. elegans X chromosome for repression by the DCC. The DCC binds to discrete, dispersed sites on X of two types. rex sites recruit the DCC in an autonomous, DNA sequence-dependent manner using a 12 bp consensus motif that is enriched on X. This motif is critical for DCC binding, is clustered in rex sites, and confers much of X-chromosome specificity. Motif variants enriched on X by 3.8-fold or more are highly predictive (95%) for rex sites. In contrast, dox sites lack the X-enriched variants and cannot bind the DCC when detached from X. dox sites are more prevalent than rex sites and, unlike rex sites, reside preferentially in promoters of some expressed genes. These findings fulfill predictions for a targeting model in which the DCC binds to recruitment sites on X and disperses to discrete sites lacking autonomous recruitment ability. To relate DCC binding to function, we identified dosage-compensated and non-compensated genes on X. Unexpectedly, many genes of both types have bound DCC, but many do not, suggesting the DCC acts over long distances to repress X gene expression. Remarkably, the DCC binds to autosomes, but at far fewer sites and rarely at consensus motifs. DCC disruption causes opposite effects on expression of X and autosomal genes. The DCC thus acts at a distance to impact expression throughout the genome. Keywords: dosage compensation, condensin, X chromosome, gene expression, epigenetics C. elegans
2009-03-01 | GSE14649 | GEO
Project description:To investigate the mechanisms mediating the inhibitory effects of DCC-2036 on LoVo, gene expression profiling analysis using data obtained from RNA-seq of LoVo cells treated with/without DCC-2036.
2025-01-15 | GSE214063 | GEO
Project description:In many species, a dosage compensation complex (DCC) is targeted to X chromosomes of one sex to equalize levels of X gene products between males (1X) and females (2X). Here we identify cis-acting regulatory elements that target the C. elegans X chromosome for repression by the DCC. The DCC binds to discrete, dispersed sites on X of two types. rex sites recruit the DCC in an autonomous, DNA sequence-dependent manner using a 12 bp consensus motif that is enriched on X. This motif is critical for DCC binding, is clustered in rex sites, and confers much of X-chromosome specificity. Motif variants enriched on X by 3.8-fold or more are highly predictive (95%) for rex sites. In contrast, dox sites lack the X-enriched variants and cannot bind the DCC when detached from X. dox sites are more prevalent than rex sites and, unlike rex sites, reside preferentially in promoters of some expressed genes. These findings fulfill predictions for a targeting model in which the DCC binds to recruitment sites on X and disperses to discrete sites lacking autonomous recruitment ability. To relate DCC binding to function, we identified dosage-compensated and non-compensated genes on X. Unexpectedly, many genes of both types have bound DCC, but many do not, suggesting the DCC acts over long distances to repress X gene expression. Remarkably, the DCC binds to autosomes, but at far fewer sites and rarely at consensus motifs. DCC disruption causes opposite effects on expression of X and autosomal genes. The DCC thus acts at a distance to impact expression throughout the genome. Keywords: dosage compensation, condensin, X chromosome, gene expression, epigenetics, C. elegans
2009-03-01 | GSE14651 | GEO
Project description:In many species, a dosage compensation complex (DCC) is targeted to X chromosomes of one sex to equalize levels of X gene products between males (1X) and females (2X). Here we identify cis-acting regulatory elements that target the C. elegans X chromosome for repression by the DCC. The DCC binds to discrete, dispersed sites on X of two types. rex sites recruit the DCC in an autonomous, DNA sequence-dependent manner using a 12 bp consensus motif that is enriched on X. This motif is critical for DCC binding, is clustered in rex sites, and confers much of X-chromosome specificity. Motif variants enriched on X by 3.8-fold or more are highly predictive (95%) for rex sites. In contrast, dox sites lack the X-enriched variants and cannot bind the DCC when detached from X. dox sites are more prevalent than rex sites and, unlike rex sites, reside preferentially in promoters of some expressed genes. These findings fulfill predictions for a targeting model in which the DCC binds to recruitment sites on X and disperses to discrete sites lacking autonomous recruitment ability. To relate DCC binding to function, we identified dosage-compensated and non-compensated genes on X. Unexpectedly, many genes of both types have bound DCC, but many do not, suggesting the DCC acts over long distances to repress X gene expression. Remarkably, the DCC binds to autosomes, but at far fewer sites and rarely at consensus motifs. DCC disruption causes opposite effects on expression of X and autosomal genes. The DCC thus acts at a distance to impact expression throughout the genome. Keywords: dosage compensation, condensin, X chromosome, gene expression, epigenetics, C. elegans
2009-03-01 | GSE14652 | GEO
Project description:In many species, a dosage compensation complex (DCC) is targeted to X chromosomes of one sex to equalize levels of X gene products between males (1X) and females (2X). Here we identify cis-acting regulatory elements that target the C. elegans X chromosome for repression by the DCC. The DCC binds to discrete, dispersed sites on X of two types. rex sites recruit the DCC in an autonomous, DNA sequence-dependent manner using a 12 bp consensus motif that is enriched on X. This motif is critical for DCC binding, is clustered in rex sites, and confers much of X-chromosome specificity. Motif variants enriched on X by 3.8-fold or more are highly predictive (95%) for rex sites. In contrast, dox sites lack the X-enriched variants and cannot bind the DCC when detached from X. dox sites are more prevalent than rex sites and, unlike rex sites, reside preferentially in promoters of some expressed genes. These findings fulfill predictions for a targeting model in which the DCC binds to recruitment sites on X and disperses to discrete sites lacking autonomous recruitment ability. To relate DCC binding to function, we identified dosage-compensated and non-compensated genes on X. Unexpectedly, many genes of both types have bound DCC, but many do not, suggesting the DCC acts over long distances to repress X gene expression. Remarkably, the DCC binds to autosomes, but at far fewer sites and rarely at consensus motifs. DCC disruption causes opposite effects on expression of X and autosomal genes. The DCC thus acts at a distance to impact expression throughout the genome. Keywords: dosage compensation, condensin, X chromosome, gene expression, epigenetics, C. elegans
2009-03-01 | GSE14653 | GEO
Project description:We searched for putative phenotypic and genotypic differences between primary lesions and melanoma metastasis. Therefore we investigated melanoma cells derived either from the primary tumor or from lymph node metastasis of the same individual patient. In vitro studies revealed high migratory and anchorage independent growth of metastasis-derived cells. Unexpectedly, whole genome DNA analysis displayed a total of 10 homozygous losses in the primum-derived cell line, whereas the metastasis–derived cell line only shared 5 of those losses. We further tested these cells in a mouse model for intradermal melanoma growth and detected fast growth of the metastasis-derived cell line and no growth of primum-derived cells. Therefore we suggest that tumor cell progression at the metastatic niche can occur parallel and independently from the primary tumor. Additionally we screened melanoma samples isolated from patients and could identify one case were the primum harboured deletions not present in the metastatic lesion. We propose that for mutation-targeted therapy genotyping should be performed not only from primary, but foremost from metastatic melanoma cells.
2011-04-07 | GSE26053 | GEO
Project description:We searched for putative phenotypic and genotypic differences between primary lesions and melanoma metastasis. Therefore we investigated melanoma cells derived either from the primary tumor or from lymph node metastasis of the same individual patient. In vitro studies revealed high migratory and anchorage independent growth of metastasis-derived cells. Unexpectedly, whole genome DNA analysis displayed a total of 10 homozygous losses in the primum-derived cell line, whereas the metastasis–derived cell line only shared 5 of those losses. We further tested these cells in a mouse model for intradermal melanoma growth and detected fast growth of the metastasis-derived cell line and no growth of primum-derived cells. Therefore we suggest that tumor cell progression at the metastatic niche can occur parallel and independently from the primary tumor. Additionally we screened melanoma samples isolated from patients and could identify one case were the primum harboured deletions not present in the metastatic lesion. We propose that for mutation-targeted therapy genotyping should be performed not only from primary, but foremost from metastatic melanoma cells. Blood samples as well tumor samples were directly processed for DNA isolation and subsequent chip hybridization. Each sample was hybridized onto a single affymetrix SNP 6.0 chip.
2011-04-07 | E-GEOD-26053 | biostudies-arrayexpress
Project description:In many species, a dosage compensation complex (DCC) is targeted to X chromosomes of one sex to equalize levels of X gene products between males (1X) and females (2X). Here we identify cis-acting regulatory elements that target the C. elegans X chromosome for repression by the DCC. The DCC binds to discrete, dispersed sites on X of two types. rex sites recruit the DCC in an autonomous, DNA sequence-dependent manner using a 12 bp consensus motif that is enriched on X. This motif is critical for DCC binding, is clustered in rex sites, and confers much of X-chromosome specificity. Motif variants enriched on X by 3.8-fold or more are highly predictive (95%) for rex sites. In contrast, dox sites lack the X-enriched variants and cannot bind the DCC when detached from X. dox sites are more prevalent than rex sites and, unlike rex sites, reside preferentially in promoters of some expressed genes. These findings fulfill predictions for a targeting model in which the DCC binds to recruitment sites on X and disperses to discrete sites lacking autonomous recruitment ability. To relate DCC binding to function, we identified dosage-compensated and non-compensated genes on X. Unexpectedly, many genes of both types have bound DCC, but many do not, suggesting the DCC acts over long distances to repress X gene expression. Remarkably, the DCC binds to autosomes, but at far fewer sites and rarely at consensus motifs. DCC disruption causes opposite effects on expression of X and autosomal genes. The DCC thus acts at a distance to impact expression throughout the genome. Keywords: dosage compensation, condensin, X chromosome, gene expression, epigenetics, C. elegans
2009-03-01 | GSE14650 | GEO