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ERK signaling plays an essential role in the IFNg-mediated apoptosis of melanoma cells.

ABSTRACT: ERK signaling plays an essential role in the IFNg-mediated apoptosis of melanoma cells.

PROVIDER: PRJNA985589 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24968301.fastq.gz	Fastqsanger.gz
	SRR24968302.fastq.gz	Fastqsanger.gz
	SRR24968303.fastq.gz	Fastqsanger.gz
	SRR24968304.fastq.gz	Fastqsanger.gz
	SRR24968305.fastq.gz	Fastqsanger.gz

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ERK signaling plays an essential role in the IFNg-mediated apoptosis of melanoma cells. [RNAseq]

Project description:Interferon-gamma (IFNg) exerts potent growth inhibitory (antiproliferative/pro-apoptotic) effects on a wide range of tumors, including melanoma. While several terminal effectors of cell cycle arrest and apoptosis have been identified, a definitive account of the signaling pathway leading to these events is lacking. We set up a chemical genomics screen and a whole genome targeting CRISPR/Cas9 screen in a growth inhibition (GI)-sensitive patient-derived melanoma (PDM) cell line. Drug screening revealed that treatment with RAF and ERK inhibitors disrupted IFNg GI in PDM cells. For the CRISPR screen, the gene-level analysis showed that the magnitude of enrichment for guide RNAs targeting ERK2 in IFNg-treated cells was comparable to core IFNg signaling proteins like IFNGR2, JAK1, JAK2, and STAT1. We validated the involvement of ERK by detecting a sustained increase in phospho-ERK1/2 (p-ERK) levels following IFNg treatment. In live imaging experiments, we found that an ERK inhibitor (ERKi) blocks the induction of cell death in 17 of 23 (~74%) IFNg-sensitive PDM lines covering all the MAPK mutant and triple wildtype molecular subtypes. Through gene expression analysis, we found that IFNg-ERK signaling triggered the expression of stress response genes and subsequent upregulation of DR5 and NOXA, which were both critical for the induction of cell death. In summary, the IFNg-ERK signaling axis mediates cell death downstream of IFNg treatment in melanoma cells. Our results provide a new understanding of the IFNg-mediated GI pathway that will also be crucial to define mechanisms of GI resistance in tumor cells.

2023-10-06 | GSE235235 | GEO

ERK signaling plays an essential role in the IFNg-mediated apoptosis of melanoma cells. [CRISPR screen]

2023-10-06 | GSE235237 | GEO

ERK signaling plays an essential role in the IFNg-mediated apoptosis of melanoma cells. [RNAseq]

Project description:ERK signaling plays an essential role in the IFNg-mediated apoptosis of melanoma cells. [RNAseq]

| PRJNA985598 | ENA

ERK signaling plays an essential role in the IFNg-mediated apoptosis of melanoma cells. [CRISPR screen]

Project description:ERK signaling plays an essential role in the IFNg-mediated apoptosis of melanoma cells. [CRISPR screen]

| PRJNA985597 | ENA

ERK signaling plays an essential role in the IFNg-mediated apoptosis of melanoma cells.

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-10-06 | GSE235238 | GEO

SOX7 regulates MAPK/ERK-BIM mediated apoptosis in cancer cells

Project description:SOX7 regulates MAPK/ERK-BIM mediated apoptosis in cancer cells

| PRJNA541940 | ENA

IFNg+ vs IFNg- Treg

Project description:Gene expression studies comparing IFNg+ Tregs versus IFNg- Tregs from human peripheral blood Ex vivo sorted Tregs (CD25highCD127neg) were stimulated for 4 hours and IFNg-secreting cells were detected by a IFNg-capture kit. The samples were resorted based on IFNg expression.

2016-07-01 | E-GEOD-71274 | biostudies-arrayexpress

SOX7 regulates MAPK/ERK-BIM mediated apoptosis in cancer cells

Project description:Here we showed that SOX7 was significantly downregulated in different cancer types, especially in lung and breast cancers. Low expression of SOX7 was associated with advanced stage of cancer with shorter overall survival. Cancer cells with loss of SOX7 promoted cell survival and colony formation, suppressed cellular apoptosis and produced a drug resistant phenotype against a variety of chemo/targeting therapeutic agents. Mechanistically, SOX7 induced cellular apoptosis through upregulation of genes associated with both P38 and apoptotic signaling pathway, as well as preventing the proteasome mediated degradation of pro-apoptotic protein BIM. Treatment of either a proteasome inhibitor MG132 or bortezomib, or with a p-ERK/MEK inhibitor U0126 attenuate the SOX7 promoted BIM degradation.

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IFNg+ vs IFNg- Treg

Project description:Gene expression studies comparing IFNg+ Tregs versus IFNg- Tregs from human peripheral blood

2016-07-01 | GSE71274 | GEO

Melanoma NRAS - Cooperative induction of apoptosis in nras mutant melanoma by inhibition of mek and rock

Project description:In the present work we propose a new therapy for NRAS mutant melanoma. Simultaneous inhibition of MEK and ROCK caused induction of BimEL , PARP, and Puma, and hence apoptosis. In vivo, MEK and ROCK inhibition suppressed growth of established tumors. Our findings warrant clinical investigation of the effectiveness of combinatorial targeting of MAPK/ERK and ROCK in NRAS mutant melanoma.

2015-03-11 | PXD000528 | Pride

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