MTSS1 Suppresses NF-kB Activity in Lung Adenocarcinoma through Repression of RelA/p65 Phosphorylation
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ABSTRACT:
PROVIDER: PRJNA744471 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15058861.fastq.gz | Fastqsanger.gz | |||
| SRR15058862.fastq.gz | Fastqsanger.gz | |||
| SRR15058863.fastq.gz | Fastqsanger.gz | |||
| SRR15058864.fastq.gz | Fastqsanger.gz | |||
| SRR15058865.fastq.gz | Fastqsanger.gz |
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Project description:Metastasis suppressor 1 (MTSS1) is a 755 amino acid protein found in the cell cytoplasm which binds to actin and promotes cytoskeleton organization and is a known suppressor of lung adenocarcinoma metastasis This study demonstrated that preservation of MTSS1 protein expression in lung adenocarcinoma was associated with a 20% 5-year survival advantage in patients. Furthermore, overexpression of MTSS1 was found to reduce metastasis and disease progression in an in-vivo orthotopic lung adenocarcinoma mouse model. Nuclear factor kappa B (NF-kB), an important nuclear transcription factor, has been shown to be constitutively active in lung adenocarcinoma and strongly associated with the development of metastasis. The NF-kB RelA/p65 subunit is involved in NF-kB heterodimer formation and subsequent nuclear translocation leading to activation of NF-kB responsive gene transcription. Phosphorylation and acetylation of p65 are critical post-translational modifications required for NF-kB activation. In this study, we demonstrate that MTSS1 expression leads to decreased NF-κB mediated gene transcription through inhibition of p65 phosphorylation. These findings uncover a novel mechanism through which MTSS1 may regulate lung adenocarcinoma metastasis by impairment of NF-κB regulated gene transcription.
2024-07-07 | GSE179644 | GEO
Project description:Aberrant regulation of NF-kB pathway is believed to be a major event contributing to malignant transformation and progression of prostate cancer (PCa). P65 consists of a DNA-binding and dimerization domain (RHD), nuclear localization signal (NLS) and transactivation domains (TA1 and TA2). The c-terminal 30 amino acids (TA1 domain) comprise the most important transactivation domain and NF-kB transactivation may be regulated by multiple phosphorylation in this domain. This p536 is located in TA1 domain and is conserved in human, mouse, chicken. We previously discovered that p536 is present in majority of PCa and associated with ERG expression indicating that ERG can significantly enhance phosphorylation of p65 at Ser536 in vivo. We have successfully generated a dominant negative (DN) p65 which has been mutated (S536A) such that it cannot be phosphorylated at Ser 536 and cannot carry out Ser536 phosphorylation dependent functions. We also generated two mutants S536D and S536E which are the phosphomimetic mutant that resembles phospho-p65 and can be detected by anti-phospho-p65 antibody. We carried out microarray studies and discovered a set of p536 regulated genes compared with wild type p65 regulated gene set.
2015-03-12 | GSE63210 | GEO
Project description:Smoking is the most important risk factor for both lung cancer (LC) and chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the role of myeloid cell NF-kB in the regulation of tumor cell growth signaling. We subjected mice lacking myeloid RelA/p65 to a metastatic LC model. Cigarette smoke (CS) exposure significantly increased the proliferation of Lewis lung carcinoma cell (LLC) tumors in wild type mice. In CS exposed mice lacking myeloid RelA/p65, the tumor growth was largely inhibited. Transcriptome and pathway analysis of cancer tissue revealed a fundamental impact of myeloid cells on various growth signaling pathways. Myeloid RelA/p65 is necessary to link smoke-induced inflammation with LC growth. Keywords: Expression profiling by array Analysis of gene expression in lewis lung carcinoma cells resected from lungs of WT and RelA/p65 deficient mice exposed to smoke or air. Four different samples were analyzed (3 replicates each).
2012-03-31 | E-GEOD-36568 | biostudies-arrayexpress
Project description:Smoking is the most important risk factor for both lung cancer (LC) and chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the role of myeloid cell NF-kB in the regulation of tumor cell growth signaling. We subjected mice lacking myeloid RelA/p65 to a metastatic LC model. Cigarette smoke (CS) exposure significantly increased the proliferation of Lewis lung carcinoma cell (LLC) tumors in wild type mice. In CS exposed mice lacking myeloid RelA/p65, the tumor growth was largely inhibited. Transcriptome and pathway analysis of cancer tissue revealed a fundamental impact of myeloid cells on various growth signaling pathways. Myeloid RelA/p65 is necessary to link smoke-induced inflammation with LC growth. Keywords: Expression profiling by array
2012-04-01 | GSE36568 | GEO
Project description:Using a mouse model with hepatocyte-specific deletion of transcription factor NF-κB RelA (p65), our group has previously revealed the important role of RelA in inducing the acute phase response, maintaining host defense, and preventing liver injury during sepsis. To goal of this study was determine the influence of RelA on hepatic gene changes that provide liver protection during infection. Mice were generated with functional deletion of NF-kappaB RelA (p56) in hepatocytes using a Cre-LoxP system. Mutant mice expressed Cre-recombinase under the transcriptional control of an albumin promotor and homozygous floxed RelA alleles. Wild type control mice lack the Cre-recombinase. Microarray analysis was performed on liver RNA collected from both genotypes of mice in the absence and presence of pneumococcal bacteremia.
2019-06-07 | GSE126642 | GEO
Project description:We reported a direct phosphorylation of the Ser547 of the RelA/p65 subunit of NF-kB by ATM kinase. A comparative transcriptomic analyse with HEK293 cells expressing exclusively HA-p65wt or a non-phosphorylable mutant HA-p65S547A was conducted to identify the genes regulated by this phosphorylation after an Etoposide treatment.
2012-05-31 | GSE33990 | GEO
Project description:A common response to physiological duress is the hepatic acute phase response, a process during which the expression of many genes is altered in the liver. Amongst these transcripts are those encoding acute phase proteins, defined as circulating proteins with significantly changed concentrations during an acute phase response. The goal of this study was to determine the influence of NF-kappaB RelA (p65) on hepatic gene changes including but not limited to acute phase proteins during bacterial pneumonia. Using the Cre-LoxP system, mice were generated with functional deletion of NF-kappaB RelA (p65) in hepatocytes. In mutant mice, Cre-recombinase was expressed under transcriptional control of an albumin promoter in the presence of homozygous floxed alleles for RelA. Wild-type control mice lacked the Cre-recombinase transgene. Microarray analysis was performed on liver RNA collected from both genotypes of mice in the absence and presence of pneumococcal pneumonia. RNA from 2 separate groups of mice (3 mice per group) was analyzed: 1) Control mice infected intratracheally for 24h with 10^6 CFU of Streptococcus pneumoniae (serotype 3); and 2) Mutant mice infected intratracheally for 24h with 10^6 CFU of Streptococcus pneumoniae (serotype 3).
2012-02-16 | E-GEOD-35513 | biostudies-arrayexpress
Project description:A common response to physiological duress is the hepatic acute phase response, a process during which the expression of many genes is altered in the liver. Amongst these transcripts are those encoding acute phase proteins, defined as circulating proteins with significantly changed concentrations during an acute phase response. The goal of this study was to determine the influence of NF-kappaB RelA (p65) on hepatic gene changes including but not limited to acute phase proteins during bacterial pneumonia. Using the Cre-LoxP system, mice were generated with functional deletion of NF-kappaB RelA (p65) in hepatocytes. In mutant mice, Cre-recombinase was expressed under transcriptional control of an albumin promoter in the presence of homozygous floxed alleles for RelA. Wild-type control mice lacked the Cre-recombinase transgene. Microarray analysis was performed on liver RNA collected from both genotypes of mice in the absence and presence of pneumococcal pneumonia.
2012-02-16 | GSE35513 | GEO
Project description:We reported a direct phosphorylation of the Ser547 of the RelA/p65 subunit of NF-kB by ATM kinase. A comparative transcriptomic analyse with HEK293 cells expressing exclusively HA-p65wt or a non-phosphorylable mutant HA-p65S547A was conducted to identify the genes regulated by this phosphorylation after an Etoposide treatment. HEK293 cells expressing exclusively HA-p65wt or HA-p65S547A were treated during four or eight hours with Etoposide or left untreated. This was performed three times to obtain independent triplicates for the microarray expermiment.
2012-05-30 | E-GEOD-33990 | biostudies-arrayexpress
Project description:Mouse livers lacking NF-kappaB RelA (p65) during bacteremia
| PRJNA522786 | ENA