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DAB2IP Loss in Luminal A Breast Cancer Leads to NF-kB- Associated Aggressive Oncogenic Phenotypes

ABSTRACT: DAB2IP Loss in Luminal A Breast Cancer Leads to NF-kB- Associated Aggressive Oncogenic Phenotypes

PROVIDER: PRJNA947218 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23932652_1.fastq.gz	Fastqsanger.gz
	SRR23932652_2.fastq.gz	Fastqsanger.gz
	SRR23932653_1.fastq.gz	Fastqsanger.gz
	SRR23932653_2.fastq.gz	Fastqsanger.gz
	SRR23932654_1.fastq.gz	Fastqsanger.gz

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DAB2IP Loss in Luminal A Breast Cancer Leads to NF-kB- Associated Aggressive Oncogenic Phenotypes

Project description:Despite proven therapy options for estrogen receptor (ER)-positive tumors, a significant number of patients with these cancers exhibit relapse with associated metastasis. Studies have shown that the loss of expression of RasGAPs leads to aggressive phenotypes and poor outcomes in several cancers including breast cancer. In our study, mining TCGA gene expression profiles of ER-positive breast tumors, we found that low expression of the RasGAP, DAB2IP is associated with a significant decrease in relapse-free survival in patients with Luminal A breast tumors. Immunostaining found that DAB2IP loss occurs in grade 2 tumors and higher. Consistent with this, genes upregulated in low DAB2IP Luminal A tumors are shared with more aggressive tumor subtypes, and are associated with proliferation, metastasis, and enhanced ER-signaling. In addition, cell-based studies reveal that low DAB2IP expression in ER-positive breast cancer cells is associated with increased proliferation, enhanced stemness phenotypes, and activation of IKK, the upstream regulator of the NF-B signaling pathway. Further, integrating cell-based ChIP-seq with motif analysis and TCGA RNA-seq data, we identify a candidate set of NF-B target genes that are upregulated with loss of DAB2IP and are proposed to regulate several oncogenic phenotypes, including altered RNA processing. This study provides new insight into mechanisms associated with aggressiveness and recurrence within a subset of Luminal A breast cancers that are otherwise typically less aggressive. Gene expression profiling by RNA-sequencing of DAB2IP knockdown and control MCF10A cells.

2024-12-18 | GSE227876 | GEO

DAB2IP Loss in Luminal A Breast Cancer Leads to NF-kB- Associated Aggressive Oncogenic Phenotypes

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DAB2IP Loss in Luminal A Breast Cancer Leads to NF-kB- Associated Aggressive Oncogenic Phenotypes

Project description:DAB2IP Loss in Luminal A Breast Cancer Leads to NF-kB- Associated Aggressive Oncogenic Phenotypes

| PRJNA947220 | ENA

DAB2IP Loss in Luminal A Breast Cancer Leads to NF-kB- Associated Aggressive Oncogenic Phenotypes

Project description:DAB2IP Loss in Luminal A Breast Cancer Leads to NF-kB- Associated Aggressive Oncogenic Phenotypes

| PRJNA947221 | ENA

DAB2IP Loss in Luminal A Breast Cancer Leads to NF-kB- Associated Aggressive Oncogenic Phenotypes

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

2024-12-18 | GSE227877 | GEO

DAB2IP loss in luminal a breast cancer leads to NF-κB-associated aggressive oncogenic phenotypes.

Project description:Despite proven therapy options for estrogen receptor-positive (ER+) breast tumors, a substantial number of patients with ER+ breast cancer exhibit relapse with associated metastasis. Loss of expression of RasGAPs leads to poor outcomes in several cancers, including breast cancer. Mining the The Cancer Genome Atlas (TCGA) breast cancer RNA-Seq dataset revealed that low expression of the RasGAP DAB2IP was associated with a significant decrease in relapse-free survival in patients with Luminal A breast cancer. Immunostaining demonstrated that DAB2IP loss occurred in grade 2 tumors and higher. Consistent with this, genes upregulated in DAB2IP-low Luminal A tumors were shared with more aggressive tumor subtypes and were associated with proliferation, metastasis, and altered ER signaling. Low DAB2IP expression in ER+ breast cancer cells was associated with increased proliferation, enhanced stemness phenotypes, and activation of IKK, the upstream regulator of the transcription factor NF-κB. Integrating cell-based ChIP-Seq with motif analysis and TCGA RNA-Seq data, we identified a set of candidate NF-κB target genes upregulated with loss of DAB2IP linked with several oncogenic phenotypes, including altered RNA processing. This study provides insight into mechanisms associated with aggressiveness and recurrence within a subset of the typically less aggressive Luminal A breast cancer intrinsic subtype.

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Effects of DAB2IP expression on gene expression in DLD1 cells

Project description:To assess the function of DAB2IP in colon cancer, we expressed DAB2IP or control LACZ in DLD1 cells which lack DAB2IP.

2023-03-05 | GSE224869 | GEO

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Project description:To study DAB2IP function on colon cancer, we depleted DAB2IP in HCT116 cells using shDAB2IP or shCNT(scramble) as a control.

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