16q22-24 DNA amplification specifically predicts and mediates, through MAF gene, breast cancer bone metastasis.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE51238 | GEO | 2014/10/01
SECONDARY ACCESSION(S): PRJNA221788
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-10-01 | E-GEOD-51238 | biostudies-arrayexpress
Project description:MAF amplification increases the risk of breast cancer (BCa) metastasis through mechanisms that are still poorly understood yet have important clinical implications. Oestrogen-receptor-positive (ER+) BCa requires oestrogen for both growth and metastasis, albeit by ill-known mechanisms. Here we integrate proteomics, transcriptomics, epigenomics, chromatin accessibility and functional assays from human and syngeneic mouse BCa models to show that MAF directly interacts with oestrogen receptor alpha (ERα), thereby promoting a unique chromatin landscape that favours metastatic spread. We identify metastasis-promoting genes that are de novo licensed following oestrogen exposure in a MAF-dependent manner. The histone demethylase KDM1A is key to the epigenomic remodelling that facilitates the expression of the pro-metastatic MAF/oestrogen-driven gene expression program, and loss of KDM1A activity prevents this metastasis. We have thus determined that the molecular basis underlying MAF/oestrogen-mediated metastasis requires genetic, epigenetic and hormone signals from the systemic environment, which influence the ability of BCa cells to metastasize.
| S-EPMC10709142 | biostudies-literature
Project description:BackgroundThere are currently no biomarkers for early breast cancer patient populations at risk of bone metastasis. Identification of mediators of bone metastasis could be of clinical interest.MethodsA de novo unbiased screening approach based on selection of highly bone metastatic breast cancer cells in vivo was used to determine copy number aberrations (CNAs) associated with bone metastasis. The CNAs associated with bone metastasis were examined in independent primary breast cancer datasets with annotated clinical follow-up. The MAF gene encoded within the CNA associated with bone metastasis was subjected to gain and loss of function validation in breast cancer cells (MCF7, T47D, ZR-75, and 4T1), its downstream mechanism validated, and tested in clinical samples. A multivariable Cox cause-specific hazard model with competing events (death) was used to test the association between 16q23 or MAF and bone metastasis. All statistical tests were two-sided.Results16q23 gain CNA encoding the transcription factor MAF mediates breast cancer bone metastasis through the control of PTHrP. 16q23 gain (hazard ratio (HR) for bone metastasis = 14.5, 95% confidence interval (CI) = 6.4 to 32.9, P < .001) as well as MAF overexpression (HR for bone metastasis = 2.5, 95% CI = 1.7 to 3.8, P < .001) in primary breast tumors were specifically associated with risk of metastasis to bone but not to other organs.ConclusionsThese results suggest that MAF is a mediator of breast cancer bone metastasis. 16q23 gain or MAF protein overexpression in tumors may help to select patients at risk of bone relapse.
| S-EPMC4681582 | biostudies-literature
Project description:MAF-amplification increases the risk of breast cancer (BCa) metastasis through poorly understood mechanisms but with important clinical implications. Estrogen receptor-positive (ER+) BCa associated with estrogen (E2) dependency sustains growth of early of breast carcinomas, but ultimately, supports metastasis by unknown mechanisms. Here we integrate proteomics, (epi)genomics and functional assays derived from human and syngeneic BCa mouse models to show that MAF directly interacts with ERalpha, thereby promoting a unique chromatin state that favors the metastatic spread of ER+ BCa cells. Indeed, we identify a set of metastasis-promoting genes that are de novo licenced following EERa2-exposure in a MAF-dependent manner. Among these we found factors influence the establishment of cellular identity and with a known role in metastasis initiation (e.g. SOX9), as well as modulators of the bone stroma, which can ultimately aid in preparing the bone metastatic “soil” (e.g. FGF18, PTHLH and JAG1). Central to the epigenomic remodeling that facilitates the expression of the MAF/E2 gene set is the histone demethylase KDM1A. Indeed, loss of KDM1A activity prevents MAF/E2-mediated BCa metastasis. Collectively, here we disentangle the molecular framework that underlies MAF/E2-mediated metastasis and demonstrate that genetic, epigenetic and hormonal systemic cues are integrated in BCa cells to determine their metastatic success, and with it patient prognosis.
2023-11-13 | PXD035936 | Pride
Project description:We performed genome-wide mapping of MAF binding sites in control and MAF-overexpressing MCF7 cells to assess the consequences of estrogen (E2) stimulation on MAF recruitment to chromatin. To this end, we cultured MCF7 cells in hormone-deprived (HD) medium for 72 h and then E2 or vehicle was added for 1h prior to chromatin immunoprecipitation (ChIP). Samples were generated in triplicate. We report that MAF binding is largely independent of E2
2023-09-15 | GSE210605 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-09-15 | GSE232389 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-09-15 | GSE210608 | GEO
Project description:We performed mRNA profiling of control and MAF-overexpressing MCF7 cells to assess the transcriptional consequences of estrogen receptor (ER) activation upon metastatic MAF expression in the presence or absence or ER (using a protac for ER degradation). To this end, we cultured MCF7 cells in hormone-deprived (HD) medium for 72 h. At this point, we treated the cells with vehice or ER-protac for 24h and then estrogen (E2) or vehicle was added for 6h prior to RNA extraction. Samples were generated in triplicate. We report that MAF supports the expression of genes involved in metastatic functions and that E2 treatment and ER expression correlates with E2 early and late gene responses and cell cycle regulation. Additionally, a set of MAF and ER-dependent gene responses was identified. Our results show that MAF expression causes an expansion of ER-mediated transcriptional events in MCF7 cells exposed to E2.
2023-09-15 | GSE232175 | GEO
Project description:We performed mRNA profiling of control and MAF-overexpressing MCF7 cells to assess the transcriptional consequences of estrogen receptor (ER) activation upon metastatic MAF expression. To this end, we cultured MCF7 cells in hormone-deprived (HD) medium for 72 h and then estrogen (E2) or vehicle was added for 6h prior to RNA extraction. Samples were generated in triplicate. We report that MAF supports the expression of genes involved in metastatic functions and that E2 treatment correlates with E2 early and late gene responses and cell cycle regulation. Additionally, a set of MAF and E2-dependent gene responses was identified. Our results show that MAF expression causes an expansion of ER-mediated transcriptional events in MCF7 cells exposed to E2. Additionally, we silenced KDM1A expression in MAF-overexpressing MCF7 cells to test whether this histone demethylase mediates the transcriptional consequences of MAF overexpression. Samples with KDM1A knockdown were generated in duplicates. We report that KDM1A partially regulates MAF/E2-dependent gene responses.
2023-09-15 | GSE210607 | GEO
Project description:We mapped chromatin accessibility on control and MAF-overexpressing MCF7 cells to assess the consequences of estrogen (E2) and metastatic MAF expression on the chromatin landscape. To this end, we cultured MCF7 cells in hormone-deprived (HD) medium for 72 h and estrogen (E2) or vehicle was added for 1h prior to DNA purification. Samples were generated in quadruplicate. We report changes in chromaitn accessibility depending on both MAF expression and E2 stimulation.
2023-09-15 | GSE210603 | GEO