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Therapeutic targeting ERRγ suppresses metastasis via extracellular matrix remodeling in small cell lung cancer

ABSTRACT: Therapeutic targeting ERRγ suppresses metastasis via extracellular matrix remodeling in small cell lung cancer

PROVIDER: PRJNA1080561 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28097737.fastq.gz	Fastqsanger.gz
	SRR28097738.fastq.gz	Fastqsanger.gz
	SRR28097739.fastq.gz	Fastqsanger.gz
	SRR28097740.fastq.gz	Fastqsanger.gz
	SRR28097741.fastq.gz	Fastqsanger.gz

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Therapeutic targeting ERRγ suppresses metastasis via extracellular matrix remodeling in small cell lung cancer (ChIP-Seq)

Project description:Small-cell lung cancer (SCLC) is the most aggressive and lethal type of lung cancer, characterized by limited treatment options, early and frequent metastasis. However, the determinants of metastasis in SCLC are poorly defined. Here, we show that estrogen-related receptor gamma (ERRγ) is overexpressed in metastatic SCLC tumors, and it is positively associated with SCLC progression. ERRγ functions as an essential activator of ECM remodeling and cell adhesion, two critical steps in metastasis, by directly regulating the expression of major genes involved in these processes. Genetic and pharmacological inhibition of ERRγ markedly reduces collagen production, cell-matrix adhesion, microfilaments production, and eventually blocks SCLC cell invasion and tumor metastasis. Notably, ERRγ antagonists significantly suppress tumor growth and metastasis and restore resistant SCLC vulnerability to chemotherapy in multiple cell-derived and patient-derived xenograft models. Taken together, these findings establish ERRγ as an attractive target for metastatic SCLC and provide a potential pharmacological strategy for treating this lethal disease.

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Therapeutic targeting ERRγ suppresses metastasis via extracellular matrix remodeling in small cell lung cancer (RNA-Seq)

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Therapeutic targeting ERRγ suppresses metastasis via extracellular matrix remodeling in small cell lung cancer (ChIP-Seq)

Project description:Therapeutic targeting ERRγ suppresses metastasis via extracellular matrix remodeling in small cell lung cancer (ChIP-Seq)

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Therapeutic targeting ERRγ suppresses metastasis via extracellular matrix remodeling in small cell lung cancer (RNA-Seq)

Project description:Therapeutic targeting ERRγ suppresses metastasis via extracellular matrix remodeling in small cell lung cancer (RNA-Seq)

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Therapeutic targeting ERRγ suppresses metastasis via extracellular matrix remodeling in SCLC

Project description:Small-cell lung cancer (SCLC) is the most aggressive and lethal type of lung cancer, characterized by limited treatment options, early and frequent metastasis. However, the determinants of metastasis in SCLC are poorly defined. Here, we show that estrogen-related receptor gamma (ERRγ) is overexpressed in metastatic SCLC tumors, and is positively associated with SCLC progression. ERRγ functions as an essential activator of extracellular matrix (ECM) remodeling and cell adhesion, two critical steps in metastasis, by directly regulating the expression of major genes involved in these processes. Genetic and pharmacological inhibition of ERRγ markedly reduces collagen production, cell-matrix adhesion, microfilament production, and eventually blocks SCLC cell invasion and tumor metastasis. Notably, ERRγ antagonists significantly suppressed tumor growth and metastasis and restored SCLC vulnerability to chemotherapy in multiple cell-derived and patient-derived xenograft models. Taken together, these findings establish ERRγ as an attractive target for metastatic SCLC and provide a potential pharmacological strategy for treating this lethal disease.

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Therapeutic targeting ERRγ suppresses metastasis via extracellular matrix remodeling in small cell lung cancer

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

2024-05-17 | GSE259273 | GEO

Specific extracellular matrix remodeling signature of colon hepatic metastases

Project description:To identify genes implicated in metastatic colonization of the liver in colorectal cancer, we collected pairs of primary tumors and hepatic metastases before chemotherapy in 13 patients. We compared mRNA expression in the pairs of patients to identify genes deregulated during metastatic evolution. We then validated the identified genes using data obtained by different groups. The 33-gene signature was able to classify 87% of hepatic metastases, 98% of primary tumors, 97% of normal colon mucosa, and 95% of normal liver tissues in six datasets obtained using five different microarray platforms. The identified genes are specific to colon cancer and hepatic metastases since other metastatic locations and hepatic metastases originating from breast cancer were not classified by the signature. Gene Ontology term analysis showed that 50% of the genes are implicated in extracellular matrix remodeling, and more precisely in cell adhesion, extracellular matrix organization and angiogenesis. Because of the high efficiency of the signature to classify colon hepatic metastases, the identified genes represent promising targets to develop new therapies that will specifically affect hepatic metastasis microenvironment. 57 samples of patients with stage IV colorectal cancer. We compared using Affymetrix chips gene expression profiles between primary tumors and hepatic metastases

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Project description:Extracellular matrix remodeling regulates glucose metabolism through TXNIP destabilization

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Microglial remodeling of the extracellular matrix promotes synapse plasticity

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Specific extracellular matrix remodeling signature of colon hepatic metastases [HG-U133B]

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