Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Opposing regulation of the STING pathway in hepatic stellate cells by NBR1 and p62 determines the progression of hepatocellular carcinoma [Quantseq]

ABSTRACT: Opposing regulation of the STING pathway in hepatic stellate cells by NBR1 and p62 determines the progression of hepatocellular carcinoma [Quantseq]

PROVIDER: PRJNA1069377 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR27732975.fastq.gz	Fastqsanger.gz
	SRR27732976.fastq.gz	Fastqsanger.gz
	SRR27732977.fastq.gz	Fastqsanger.gz
	SRR27732978.fastq.gz	Fastqsanger.gz
	SRR27732979.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 24

Similar Datasets

Opposing regulation of the STING pathway in hepatic stellate cells by NBR1 and p62 determines the progression of hepatocellular carcinoma [Quantseq]

Project description:Hepatocellular carcinoma (HCC) emerges from chronic inflammation to which activation of hepatic stellate cells (HSCs) contributes by shaping a pro-tumorigenic microenvironment. Key to this process is p62, whose inactivation leads to enhanced hepatocarcinogenesis. Here, we show that while p62 positively regulates STING ubiquitination by TRIM32 by displacing NBR1, which results in the activation of the interferon (IFN) cascade, NBR1 prevents TRIM32 interaction with and the activation of STING, leading to impaired IFN synthesis. NBR1 also antagonizes STING function by promoting its trafficking from the Golgi to the endosome-lysosomal degradative cascade independent of autophagy. Importantly, NBR1 deletion completely reverts the tumor-promoting function of p62-deficient HSCs. The upregulation of the STING-IFN pathway by NBR1 deficiency enhances the anti-tumor response mediated by CD8+ T cells. These results identify NBR1 as a synthetic vulnerability of p62-deficiency in HSCs. NBR1 loss, by promoting the STING/IFN pathway, boosts anti-tumor CD8+ T cell responses to restrain HCC.

2024-10-22 | GSE254277 | GEO

Opposing regulation of the STING pathway in hepatic stellate cells by NBR1 and p62 determines the progression of hepatocellular carcinoma [RNAseq]

2024-10-22 | GSE254276 | GEO

Opposing regulation of the STING pathway in hepatic stellate cells by NBR1 and p62 determines the progression of hepatocellular carcinoma [RNAseq]

Project description:Opposing regulation of the STING pathway in hepatic stellate cells by NBR1 and p62 determines the progression of hepatocellular carcinoma [RNAseq]

| PRJNA1069376 | ENA

p62/SQSTM1 by binding to vitamin D receptor inhibits hepatic stellate cell activity, fibrosis and liver cancer

Project description:Hepatic stellate cells (HSC) play critical roles in liver fibrosis and hepatocellular carcinoma (HCC). Vitamin D receptor (VDR) activation in HSC inhibits liver inflammation and fibrosis. Here we show that p62/SQSTM1, a protein that is upregulated in liver parenchymal cells but downregulated in HCC-associated HSC, negatively regulates HSC activation. Total body or HSC-specific p62 ablation potentiates HSC activation and enhances inflammation, fibrosis and HCC progression. We demonstrate that p62 directly interacts with VDR and RXR promoting their heterodimerization, which is critical for VDR:RXR target genes recruitment. Loss of p62 in HSC impairs the repression of fibrosis and inflammation by VDR agonists. This demonstrates that p62 is a negative regulator of liver inflammation and fibrosis through its ability to promote VDR signaling in HSC, whose activation supports HCC development.

2016-11-23 | GSE78760 | GEO

The lactate-NAD axis activate cancer associated fibroblasts by downregulating p62 [Quantseq]

Project description:The lactate-NAD axis activate cancer associated fibroblasts by downregulating p62 [Quantseq]

| PRJNA779992 | ENA

The lactate-NAD axis activate cancer associated fibroblasts by downregulating p62 [Quantseq]

Project description:Reduced p62 levels are associated with the induction of the cancer-associated fibroblast (CAF) phenotype, which promotes tumorigenesis in vitro and in vivo through inflammation and metabolic reprogramming. However, how p62 is downregulated in the stroma fibroblasts by tumor cells to drive CAF activation is an unresolved central issue in the field. Here we show that tumor-secreted lactate downregulate p62 transcriptionally through a mechanism involving reduction of the NAD+/NADH ratio, which impaired poly(ADP-Ribose)-polymerase 1 (PARP1) activity. PARP1 inhibition blocked the poly(ADP-ribosyl)ation of the AP1 transcription factors, c-FOS and c-JUN, which is an obligate step for p62 downregulation. Importantly, restoring p62 levels in CAFs by NAD+ rendered CAFs less active. PARP inhibitors, such as Olaparib, mimicked lactate in the reduction of stromal p62 levels, as well as the subsequent stromal activation both in vitro and in vivo, which suggests that therapies utilizing Olaparib would benefit from strategies aimed at inhibiting CAF activity.

2022-05-16 | GSE188717 | GEO

Opposing Roles of Hepatic Stellate Cell Subpopulations in Hepatocarcinogenesis

Project description:Opposing Roles of Hepatic Stellate Cell Subpopulations in Hepatocarcinogenesis

| PRJNA873690 | ENA

p62 sustains a protumorigenic gene signature in melanoma opposing mRNA-dependent decay

Project description:p62 sustains a protumorigenic gene signature in melanoma opposing mRNA-dependent decay

| PRJNA389739 | ENA

p62 sustains a protumorigenic gene signature in melanoma opposing mRNA-dependent decay [UACC62_6days]

Project description:Metastasis is a common cancer hallmark which however, may be acquired by tumor-type specific mechanisms. Here we identify p62/SQSTM1 as a modulator of metastatic genes selectively enriched in melanoma. Loss- and gain-of-function analyses of p62 effectors revealed FERMT2 as an indicator of poor patient prognosis. Analyses in tumor cells, clinical biopsies and genetically-engineered mice (to compare p62 vs. ATG5) demonstrated that known p62 roles in autophagy and stress responses were not essential in melanomas. Instead, a genome-wide transcriptomic/proteomic/interactomic approach demonstrated that p62 controls FERMT2 and yet additional pro-metastatic genes by modulating transcript stability. This function of p62 was exerted by recruiting RNA-binding proteins, here exemplified by IGF2BP1. These data illustrate how genetically altered cancers can coordinately fuel pro-metastatic signatures.

2018-07-05 | GSE99832 | GEO

p62 sustains a protumorigenic gene signature in melanoma opposing mRNA-dependent decay [UACC62_3days]

2018-07-05 | GSE99831 | GEO