Sialic acid blockade inhibits the metastatic spread of prostate cancer to bone
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ABSTRACT:
PROVIDER: PRJNA989249 | ENA |
REPOSITORIES: ENA
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Project description:To identify signalling pathways altered by GSM6829 in prostate cancer cells, we established DU145 stable cell lines in which ST6GAL1 was overexpressed. We then performed differential gene expression, Gene Ontology and GSEA analyses using data obtained from RNA-seq of the control and OE cell lines.
2024-12-31 | GSE236208 | GEO
Project description:The inherent ability of melanoma cells to alter the differentiation-associated transcriptional repertoire to evade treatment and facilitate metastatic spread is well accepted and has been termed phenotypic switching. However, how these facets of cellular behavior are controlled remains largely elusive. Here we show that cysteine availability, whether from lysosomes (CTNS-dependent) or exogenously derived (SLC7A11-dependent or as N-acetylcysteine), controls melanoma differentiation-associated pathways by acting on the melanocyte master regulator MITF. Functional data indicate that low cysteine availability reduces MITF levels and impairs lysosome functions, which affects tumor ferroptosis sensitivity but improves metastatic spread in vivo. Mechanistically, cysteine-restrictive conditions reduce acetyl-CoA levels to decrease p300-mediated H3K27 acetylation at the melanocyte-restricted MITF promoter, thus forming a cysteine feed-forward regulation that controls MITF levels and downstream lysosome functions. These findings collectively suggest that cysteine homeostasis governs melanoma differentiation by maintaining MITF levels and lysosome functions, which protect against ferroptosis and limit metastatic spread.
2024-08-16 | GSE269922 | GEO
Project description:The metastatic spread of breast cancer accelerates during sleep
| PRJNA746552 | ENA
Project description:Metastatic spread in Ewing Tumors (ET) is hematogenous and malignant features have been shown to correlate with hypoxia and angiogenesis. We identified several Ewing tumor specific genes (Staege MS et al. Cancer Res. 2004;64:8213-21). Microarray analysis confirmed an endothelial signature of this tumor and revealed the G-protein coupled receptor-64 (GPR64), an orphan receptor with normal expression restricted to human epididymis, to be highly induced in ET. Down-regulation of GPR64 in ET lines by RNA interference did not reduce their proliferative capacity in vitro as measured by plastic adherence dependent proliferation or contact independent growth in colony forming assays. Of interest inhibition of GPR64 expression in ET cell lines resulted in impaired endothelial differentiation in tube formation assays. Furthermore, GPR64 suppression substantially inhibited tumor growth and metastatic spread in immunodeficient Rag2-/-gammaC-/- mice. Microarray analysis of ET after GPR64 knock down revealed a GPR64-mediated induction of VEGF receptor 1 ligand placental growth factor (PGF) in ET. PGF itself was induced by EWS-FLI1 in mesenchymal stem cells. Repression of PGF expression in ET cell lines resulted in a similar phenotype as observed after GPR64 knockdown. GPR64 as well as PGF knock down correlated with a reduced proteolytic activity of Matrix Metalloproteinase MMP1 and invasiveness in vitro. MMP1 specific knock down resulted in the abrogation of metastasis of ET in Rag2-/-gammaC-/- mice. We conclude, that GPR64 and subsequent PGF up-regulation in ET orchestrate and promote endothelial invasiveness and metastatic spread and play a pivotal role in the pathogenesis and aggressiveness of this tumor. Established Ewing tumor cell lines were transfected with siRNA with specificity for CHM1 (control) or GPR64. RNA was extracted and hybridized with Affymetrix HG_U133A microarrays.
2011-09-29 | E-GEOD-23058 | biostudies-arrayexpress
Project description:The metastatic spread of cancer is achieved by the haematogenous dissemination of circulating tumour cells (CTCs). Generally, however, the temporal dynamics that dictate the generation of metastasis-competent CTCs are largely uncharacterized, and it is often assumed that CTCs are constantly shed from growing tumours or are shed as a consequence of mechanical insults1. Here we observe a striking and unexpected pattern of CTC generation dynamics in both patients with breast cancer and mouse models, highlighting that most spontaneous CTC intravasation events occur during sleep. Further, we demonstrate that rest-phase CTCs are highly prone to metastasize, whereas CTCs generated during the active phase are devoid of metastatic ability. Mechanistically, single-cell RNA sequencing analysis of CTCs reveals a marked upregulation of mitotic genes exclusively during the rest phase in both patients and mouse models, enabling metastasis proficiency. Systemically, we find that key circadian rhythm hormones such as melatonin, testosterone and glucocorticoids dictate CTC generation dynamics, and as a consequence, that insulin directly promotes tumour cell proliferation in vivo, yet in a time-dependent manner. Thus, the spontaneous generation of CTCs with a high proclivity to metastasize does not occur continuously, but it is concentrated within the rest phase of the affected individual, providing a new rationale for time-controlled interrogation and treatment of metastasis-prone cancers.
2022-04-25 | GSE180097 | GEO
Project description:Metastatic spread in Ewing Tumors (ET) is hematogenous and malignant features have been shown to correlate with hypoxia and angiogenesis. We identified several Ewing tumor specific genes (Staege MS et al. Cancer Res. 2004;64:8213-21). Microarray analysis confirmed an endothelial signature of this tumor and revealed the G-protein coupled receptor-64 (GPR64), an orphan receptor with normal expression restricted to human epididymis, to be highly induced in ET. Down-regulation of GPR64 in ET lines by RNA interference did not reduce their proliferative capacity in vitro as measured by plastic adherence dependent proliferation or contact independent growth in colony forming assays. Of interest inhibition of GPR64 expression in ET cell lines resulted in impaired endothelial differentiation in tube formation assays. Furthermore, GPR64 suppression substantially inhibited tumor growth and metastatic spread in immunodeficient Rag2-/-gammaC-/- mice. Microarray analysis of ET after GPR64 knock down revealed a GPR64-mediated induction of VEGF receptor 1 ligand placental growth factor (PGF) in ET. PGF itself was induced by EWS-FLI1 in mesenchymal stem cells. Repression of PGF expression in ET cell lines resulted in a similar phenotype as observed after GPR64 knockdown. GPR64 as well as PGF knock down correlated with a reduced proteolytic activity of Matrix Metalloproteinase MMP1 and invasiveness in vitro. MMP1 specific knock down resulted in the abrogation of metastasis of ET in Rag2-/-gammaC-/- mice. We conclude, that GPR64 and subsequent PGF up-regulation in ET orchestrate and promote endothelial invasiveness and metastatic spread and play a pivotal role in the pathogenesis and aggressiveness of this tumor.
2011-09-30 | GSE23058 | GEO
Project description:Bifidobacteria constitute a specific group of commensal bacteria which inhabit the gastrointestinal tract of humans and other mammals. Bifidobacterium breve UCC2003 has previously been shown to utilise several plant-derived carbohydrates that include cellodextrins, starch and galactan. In the current study, we investigate the ability of this strain to utilise the mucin- and human milk oligosaccharide (HMO)-derived carbohydrate, sialic acid. Using a combination of transcriptomic and functional genomic approaches, we identified a gene cluster dedicated to the uptake and metabolism of sialic acid. Furthermore, we demonstrate that B. breve UCC2003 can cross feed on sialic acid derived from the metabolism of 3’ sialyllactose, a HMO, by Bifidobacterium bifidum PRL2010.
2014-05-29 | GSE56291 | GEO
Project description:Accumulating data support the concept that ionizing radiation therapy (RT) has the potential to convert the tumor into an in situ, individualized vaccine; however this potential is rarely realized by RT alone. Transforming growth factor β (TGFβ) is an immunosuppressive cytokine that is activated by RT and inhibits the antigen-presenting function of dendritic cells and the differentiation of effector CD8+ T cells. Here we tested the hypothesis that TGFβ hinders the ability of RT to promote anti-tumor immunity. Development of tumor-specific immunity was examined in a pre-clinical model of metastatic breast cancer. Mice bearing established 4T1 mouse mammary carcinoma treated with pan-isoform specific TGFβ neutralizing antibody, 1D11, showed significantly improved control of the irradiated tumor and non-irradiated metastases, but no effect in the absence of RT. Notably, whole tumor transcriptional analysis demonstrated the selective upregulation of genes associated with immune-mediated rejection only in tumors of mice treated with RT+TGFβ blockade. Mice treated with RT+TGFβ blockade exhibited cross-priming of CD8+ T cells producing IFNγ in response to three tumor-specific antigens in tumor-draining lymph nodes, which was not evident for single modality treatment. Analysis of the immune infiltrate in mouse tumors showed a significant increase in CD4+ and CD8+ T cells only in mice treated with the combination of RT+TGFβ blockade. Depletion of CD4+ or CD8+ T cells abrogated the therapeutic benefit of RT+TGFβ blockade. These data identify TGFβ as a master inhibitor of the ability of RT to generate an in situ tumor vaccine, which supports testing inhibition of TGFβ during radiotherapy to promote therapeutically effective anti-tumor immunity. We used genome-wide microarray to depict main biological processes responsibles for the therapeutic benefit of the combination ofTGF-beta blockade and local radiotherapy. To gain a more comprehensice protrait of the effects of RT and TGFbeta blockade on gene expressionin tumors, we collected 4T1 tumors 4 days after completion of RT. Three tumors from each group were then subjected to RNA extraction and hybridization on affymetrix array.
2015-04-12 | E-GEOD-61208 | biostudies-arrayexpress
Project description:Feed-forward Cysteine Regulation Maintains Melanoma Differentiation State and Limits Metastatic Spread
| PRJNA1124125 | ENA
Project description:SHP2 Blockade Sensitizes Metastatic Triple Negative Breast Cancer to PI3K Inhibition
| PRJNA526210 | ENA