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STAT3 phosphorylation at serine 727 activates specific genetic programs and promotes clear cell renal cell carcinoma (ccRCC) aggressiveness

ABSTRACT: STAT3 phosphorylation at serine 727 activates specific genetic programs and promotes clear cell renal cell carcinoma (ccRCC) aggressiveness

PROVIDER: PRJNA1030296 | ENA |

REPOSITORIES: ENA

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STAT3 phosphorylation at serine 727 activates specific genetic programs and promotes clear cell renal cell carcinoma (ccRCC) aggressiveness

Project description:The signal transducer and activator of transcription 3 (STAT3) is a transcription factor mainly activated by phosphorylation in either tyrosine 705 (Y705) or serine 727 (S727) residues that regulates essential processes such as cell differentiation, apoptosis inhibition, or cell survival. we used microarrays to evaluate the effects of the STAT3 phosphomutants on global gene expression and identify the genes and pathways regulated by different STAT3 phosphorylation states in the 769-P cell line.

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Clear cell renal cell carcinoma (ccRCC) samples

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2017-08-08 | GSE73731 | GEO

STAT3 Serine 727 Phosphorylation: A Relevant Target to Radiosensitize Human Glioblastoma.

Project description:Radiotherapy is an essential component of glioma standard treatment. Glioblastomas (GBM), however, display an important radioresistance leading to tumor recurrence. To improve patient prognosis, there is a need to radiosensitize GBM cells and to circumvent the mechanisms of resistance caused by interactions between tumor cells and their microenvironment. STAT3 has been identified as a therapeutic target in glioma because of its involvement in mechanisms sustaining tumor escape to both standard treatment and immune control. Here, we studied the role of STAT3 activation on tyrosine 705 (Y705) and serine 727 (S727) in glioma radioresistance. This study explored STAT3 phosphorylation on Y705 (pSTAT3-Y705) and S727 (pSTAT3-S727) in glioma cell lines and in clinical samples. Radiosensitizing effect of STAT3 activation down-modulation by Gö6976 was explored. In a panel of 15 human glioma cell lines, we found that the level of pSTAT3-S727 was correlated to intrinsic radioresistance. Moreover, treating GBM cells with Gö6976 resulted in a highly significant radiosensitization associated to a concomitant pSTAT3-S727 down-modulation only in GBM cell lines that exhibited no or weak pSTAT3-Y705. We report the constitutive activation of STAT3-S727 in all GBM clinical samples. Targeting pSTAT3-S727 mainly in pSTAT3-Y705-negative GBM could be a relevant approach to improve radiation therapy.

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STAT3 phosphorylation at tyrosine 705 and serine 727 differentially regulates mouse ESC fates.

Project description:STAT3 can be transcriptionally activated by phosphorylation of its tyrosine 705 or serine 727 residue. In mouse embryonic stem cells (mESCs), leukemia inhibitory factor (LIF) signaling maintains pluripotency by inducing JAK-mediated phosphorylation of STAT3 Y705 (pY705). However, the function of phosphorylated S727 (pS727) in mESCs remains unclear. In this study, we examined the roles of STAT3 pY705 and pS727 in regulating mESC identities, using a small molecule-based system to post-translationally modulate the quantity of transgenic STAT3 in STAT3(-/-) mESCs. We demonstrated that pY705 is absolutely required for STAT3-mediated mESC self-renewal, while pS727 is dispensable, serving only to promote proliferation and optimal pluripotency. S727 phosphorylation is regulated directly by fibroblast growth factor/Erk signaling and crucial in the transition of mESCs from pluripotency to neuronal commitment. Loss of S727 phosphorylation resulted in significantly reduced neuronal differentiation potential, which could be recovered by a S727 phosphorylation mimic. Moreover, loss of pS727 sufficed LIF to reprogram epiblast stem cells to naïve pluripotency, suggesting a dynamic equilibrium of STAT3 pY705 and pS727 in the control of mESC fate.

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Project description:We demonstrated an increase in MBOAT7 and downstream phosphatidylinositol products in ccRCC. This RNAseq was of two loss of function clones and wild-type in the Caki-1 cell model (ccRCC cell line).

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LncRNA from metastatic clear cell renal cell carcinoma (ccRCC) compared with non-metastatic clear cell renal carcinoma

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Zea mays cultivar:RSQ-727

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Expression data for HIF1alpha-regulated genes in clear cell renal carcinoma cells (ccRCC)

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Project description:Genome wide DNA methylation profiling of clear cell renal cell carcinoma (ccRCC) tissue versus matched normal kidney tissue. TheÂ IlluminaÂ Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximatelyÂ 450,000 CpGs in tumor and adjacent normal kidney tissue samples from ccRCC patients. Samples included 46 paired fresh frozen ccRCC tumor and adjacent normal kidney tissues. Bisulphite converted DNA from the 92 samples were hybridised to the Illumina Infinium 450 Human Methylation Beadchip v1.2

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