Inhibition of TNBC metastasis by Gpx1
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE126675 | GEO | 2019/11/30
REPOSITORIES: GEO
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Project description:Inhibition of TNBC metastasis by Gpx1
| PRJNA522914 | ENA
Project description:Here, using mouse squamous cell carcinoma cells, we report a completely new function for the autophagy protein Ambra1 as the first described ‘spatial rheostat’ controlling the Src/FAK pathway. Ambra1 regulates the targeting of active phospho-Src away from focal adhesions into autophagic structures that cancer cells use to survive adhesion stress. Ambra1 binds to both FAK and Src in cancer cells. When FAK is present, Ambra1 is recruited to focal adhesions, promoting FAK-regulated cancer cell direction-sensing and invasion. However, when Ambra1 cannot bind to FAK, abnormally high levels of phospho-Src and phospho-FAK accumulate at focal adhesions, positively regulating adhesion and invasive migration. Spatial control of active Src requires the trafficking proteins Dynactin 1 and IFITM3, which we identified as Ambra1 binding partners by interaction proteomics. We conclude that Ambra1 is a core component of an intracellular trafficking network linked to tight spatial control of active Src and FAK levels, and so crucially regulates their cancer-associated biological outputs.
2017-04-04 | PXD006002 | Pride
Project description:p130Cas (Cas, Crk-associated substrate) is an adaptor molecule composed of an N-terminal Src homology 3 (SH3) domain, a substrate domain (SD), and a C-terminal Src binding domain (SBD). The SH3 domain of Cas has been shown to associate with various signaling molecules, including focal adhesion kinase (FAK), but its role in cellular function remains unclear. To address this issue, we established and analyzed primary fibroblasts derived from mice expressing a truncated Cas lacking the exon 2 encoding the SH3 domain (Cas exon 2â/â). In comparison to wild-type (Cas exon 2+/+) cells, Cas exon 2â/â primary fibroblasts showed delayed migration in wound healing and reduced spreading on fibronectin (FN), which would be due to reduced complex formation of Cas exon 2â/â with FAK and CrkII and also to impaired localization of Cas exon 2â/â to focal adhesions on FN. In addition, to analyze downstream signaling pathway regulated by Cas exon 2, we compared gene expression profiles between Cas exon 2+/+ and Cas exon 2â/â cells by a microarray analysis. Interestingly, we found that Cas exon 2-deficiency upregulated expression of CXC Chemokine Receptor-4 (CXCR4), CC Chemokine Receptor-5 (CCR5), and thrombospondin 4, which are implicated in cell motility and adhesion. These results define the role of Cas SH3-encoding exon in cell motility, FAK/Cas/CrkII complex formation, recruitment of Cas to focal adhesions, and regulation of cell adhesion-associated gene expression in primary fibroblasts. Experiment Overall Design: RNA samples extracted from Cas exon 2+/+, Cas exon 2+/â, and Cas exon 2â/â fibroblasts (12.5dpc, two embryos for each genotype) were labeled and hybridized on Affymetrix microarray. Gene expression patterns of Cas exon 2â/â fibroblasts were compared with those of Cas exon 2+/+ and Cas exon 2+/â cells.
2008-06-16 | E-GEOD-8357 | biostudies-arrayexpress
Project description:The expression levels of JMJD6 and its correlation with H2A.XY39ph differed in TNBC and non-TNBC cells. In addition, we have previously shown that H2A.XY39ph levels are positively correlated with tumor size, histological grade and advanced TNM stage in breast cancer. To analyze the role of JMJD6 in regulating the characteristics of different subtypes of breast cancer, the transcriptomes of TNBC cells (SUM159) and non-TNBC cells (HCC1569) that overexpressed JMJD6 were compared. We speculate that JMJD6 overexpression cause autophagy pathway activation in TNBC via enhancing ATG genes expression.
2023-10-01 | E-MTAB-6517 | biostudies-arrayexpress
Project description:p130Cas (Cas, Crk-associated substrate) is an adaptor molecule composed of an N-terminal Src homology 3 (SH3) domain, a substrate domain (SD), and a C-terminal Src binding domain (SBD). The SH3 domain of Cas has been shown to associate with various signaling molecules, including focal adhesion kinase (FAK), but its role in cellular function remains unclear. To address this issue, we established and analyzed primary fibroblasts derived from mice expressing a truncated Cas lacking the exon 2 encoding the SH3 domain (Cas exon 2∆/∆). In comparison to wild-type (Cas exon 2+/+) cells, Cas exon 2∆/∆ primary fibroblasts showed delayed migration in wound healing and reduced spreading on fibronectin (FN), which would be due to reduced complex formation of Cas exon 2∆/∆ with FAK and CrkII and also to impaired localization of Cas exon 2∆/∆ to focal adhesions on FN. In addition, to analyze downstream signaling pathway regulated by Cas exon 2, we compared gene expression profiles between Cas exon 2+/+ and Cas exon 2∆/∆ cells by a microarray analysis. Interestingly, we found that Cas exon 2-deficiency upregulated expression of CXC Chemokine Receptor-4 (CXCR4), CC Chemokine Receptor-5 (CCR5), and thrombospondin 4, which are implicated in cell motility and adhesion. These results define the role of Cas SH3-encoding exon in cell motility, FAK/Cas/CrkII complex formation, recruitment of Cas to focal adhesions, and regulation of cell adhesion-associated gene expression in primary fibroblasts. Keywords: SH3-encoding exon, p130Cas
2007-12-31 | GSE8357 | GEO
Project description:Defects in cell-cell contacts have been proposed to participate in early steps of tumor metastasis1 but little is known about the signals from the cancer cell niche that influence this process. Here, we show that the lack of adherens junctions caused by genetic loss of the adhesion molecule NECTIN1 in melanoma promotes tumor dissemination specifically under growth factor deprivation. We found that NECTIN1 was deleted in 53% of human melanomas and that its loss was enriched in metastases. NECTIN1 inactivation in zebrafish melanomas stimulated cancer cell spreading in vivo, while in human cell lines, it increased cell migration specifically in response to serum starvation. We further identified IGF1 as the serum component responsible for this effect. Serum withdrawal or IGF1 inhibition induced formation of strong adherens junctions between NECTIN1-wild-type melanoma cells. In contrast, NECTIN1-deficient cells were unable to establish adherens junctions and instead activated integrin-mediated motility through a FAK/SRC axis. During melanoma dissemination, NECTIN1 loss thus causes a cellular phenotypic switch from cell-cell adhesion to cell-matrix adhesion triggered by IGF1 signaling. Our study uncovers a mechanism by which cancer cells integrate information from the tumor microenvironment and cell-cell contacts to regulate their migratory behavior during spreading.
2022-05-26 | GSE149481 | GEO
Project description:In this study, we investigated how nicotinamide (NAM) affects cellular metabolism in TNBC cells and also such altered cellular metabolism by NAM is linked to cytotoxic functions through an integrated analysis of proteome and transcriptome data generated from three different TNBC cell lines, BT20, MB468, and MB231. By analyzing mRNA-seq data from control and NAM treated TNBC cells (3 replicates in each of 3 cell lines), we identified differentially expressed genes (DEGs), and associated cellular process. The up-regulated genes were associated with the processes related to cell death (programmed cell death, autophagy, and apoptotic mitochondrial changes) and mitochondria (organization, pH reduction/oxidation-reduction/NADP metabolism, response to starvation, respiratory chain, and lipid/oxoacid metabolism). On the other hand, the processes related to immune response (NF-kB and MAPK signaling, cell adhesion/migration, and response to cytokine) and cell proliferation were down-regulated consistently in the three TNBC cells.
2021-04-22 | GSE172494 | GEO
Project description:We describe a function of focal adhesion kinase (FAK) in driving anti-tumor immune evasion. The kinase activity of nuclear-targeted FAK in squamous cancer cells drives exhaustion of CD8+ T-cells and recruitment of regulatory T-cells by transcriptionally regulating chemokine/cytokine and ligand-receptor networks, including transcription of Ccl5 that is crucial. These changes inhibit antigen-primed cytotoxic CD8+ T-cell activity, permitting growth of FAK-expressing tumors. To address how FAK activity in squamous cell carcinoma (SCC) cancer cells promotes elevated intra-tumoral regulatory T-cells, we analyzed global transcriptional profiles of SCC cells expressing or not expressing FAK.
2015-09-29 | GSE71662 | GEO
Project description:We found that the cancer testis antigen, ZNF165, is required for viability and can modulate TGFβ-induced gene expression in mesenchymal, Claudin-Low, TNBC. We employed the Affymetrix microarray platform to uncover transcriptionally modulated genes following ZNF165 depletion and TGFβ stimulation using the Claudin-low TNBC tumor-derived cell lines, SUM159 as a model. Our results provide insight into how ZNF165 globally modulates TGFβ signaling. We used microarray analysis to uncover the transcriptional network controlled by ZNF165 and clarify the role of ZNF165 in global TGFβ signaling SUM159 and WHIM12 cells were reverse transfected with either non-targeting or ZNF165 siRNA. For SUM159 cells, sixty hours post-transfection, cells were exposed to TGFβ for 3 hours. For WHIM12, forty eight hours post-transfection, cells were exposed to TGFβ for 3 hours. Total RNA was isolated and hybridized on to Affymetrix microarrays. Each experiment was repeated three times.
2015-11-09 | E-GEOD-63984 | biostudies-arrayexpress
Project description:two luminal cell lines were added, MCF7 and BT-474 two TNBC cell line were added, MB231 and BT-549 microRNA expression profiles were conpared between the luminal group and the TNBC group
2014-10-03 | E-GEOD-62022 | biostudies-arrayexpress