Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis

ABSTRACT: The cohesin complex is a critical regulator of gene expression. STAG2 is the most frequently mutated cohesin subunit across several cancer types and is a key tumor suppressor in lung cancer. Here, we coupled somatic CRISPR-Cas9 genome editing and tumor barcoding with an autochthonous oncogenic KRAS-driven lung cancer model and show that STAG2 is uniquely tumor suppressive among all core and auxiliary cohesin components. The heterodimeric complex components PAXIP1 and PAGR1 have highly correlated effects with STAG2 in human lung cancer cell lines, are tumor suppressors in vivo, and are epistatic to STAG2 in oncogenic KRAS-driven lung tumorigenesis in vivo. STAG2 inactivation elicits changes in gene expression, chromatin accessibility, and 3D genome confirmation that impact cancer cell state. Gene expression and chromatin accessibility similarities between STAG2- and PAXIP1-deficient neoplastic cells further relates STAG2-cohesin to PAXIP1/PAGR1. These findings reveal a STAG2-PAXIP1/PAGR1 tumor-suppressive axis and uncover novel PAXIP1-dependent and PAXIP1-independent STAG2-cohesin mediated mechanisms of lung tumor suppression.

ORGANISM(S): Mus musculus

PROVIDER: GSE277290 | GEO | 2024/10/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis [ATAC-Seq]

Project description:The cohesin complex is a critical regulator of gene expression. STAG2 is the most frequently mutated cohesin subunit across several cancer types and is a key tumor suppressor in lung cancer. Here, we coupled somatic CRISPR-Cas9 genome editing and tumor barcoding with an autochthonous oncogenic KRAS-driven lung cancer model and show that STAG2 is uniquely tumor suppressive among all core and auxiliary cohesin components. The heterodimeric complex components PAXIP1 and PAGR1 have highly correlated effects with STAG2 in human lung cancer cell lines, are tumor suppressors in vivo, and are epistatic to STAG2 in oncogenic KRAS-driven lung tumorigenesis in vivo. Gene expression and chromatin accessibility similarities between STAG2- and PAXIP1-deficient neoplastic cells further relates STAG2-cohesin to PAXIP1/PAGR1. These findings reveal a STAG2-PAXIP1/PAGR1 tumor-suppressive axis and uncover novel PAXIP1-dependent and PAXIP1-independent STAG2-cohesin mediated mechanisms of lung tumor suppression.

2024-10-22 | GSE274205 | GEO

A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis [RNA-Seq]

2024-10-22 | GSE274204 | GEO

PAXIP1 and STAG2 converge to maintain 3D genome archi-tecture and facilitate promoter/enhancer contacts to enable stress hormone-dependent transcription

Project description:How steroid hormone receptors (SHRs) orchestrate transcriptional activity remains only partly understood. Upon activation, SHRs bind the genome and recruit their co-regulators, crucial to induce gene expression. However, it remains unknown which components of the SHR-recruited coregulator complex are essential to drive transcription following hormonal stimuli. Through a FACS-based genome-wide CRISPR screen, we comprehensively dissected the Glucocorticoid Receptor (GR) co-regulatory complex involved in gene-target regulation. We describe a novel functional cross-talk between PAXIP1 and the cohesin subunit STAG2 that is critical for regulation of gene expression by GR. Without altering the GR cistrome, PAXIP1 and STAG2 depletion alter the GR transcriptome, by impairing the recruitment of 3D-genome organization proteins to the GR complex. Importantly, we demonstrate that PAXIP1 is required for stability of cohesin on the genome, its localization to GR-occupied sites, and maintenance of enhancer-promoter interactions. Moreover, in lung cancer, where GR acts as tumor suppressor, PAXIP1/STAG2 loss enhances GR-mediated tumor suppressor activity by modifying local chromatin interactions. All together, we introduce PAXIP1 and STAG2 as novel co-regulators of GR, required to maintain 3D-genome architecture and drive the GR transcriptional programme following hormonal stimuli.

2023-10-24 | PXD038902 | Pride

PAXIP1 and STAG2 converge to maintain 3D genome architecture and facilitate promoter/enhancer contacts to enable stress hormone-dependent transcription [CRISPR_screen]

2023-07-22 | GSE237953 | GEO

PAXIP1 and STAG2 converge to maintain 3D genome architecture and facilitate promoter/enhancer contacts to enable stress hormone-dependent transcription [ChIP-seq]

2023-07-11 | GSE221915 | GEO

PAXIP1 and STAG2 converge to maintain 3D genome architecture and facilitate promoter/enhancer contacts to enable stress hormone-dependent transcription [4C-seq]

2023-07-11 | GSE221914 | GEO

PAXIP1 and STAG2 converge to maintain 3D genome architecture and facilitate promoter/enhancer contacts to enable stress hormone-dependent transcription [RNA-seq]

2023-07-11 | GSE221916 | GEO

A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis

Project description:A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis

| PRJNA1161652 | ENA

Disruption of STAT3 signaling promotes KRAS induced lung tumorigenesis

Project description:Oncogenic STAT3 functions are known in various malignancies. We found that STAT3 plays an unexpected tumor suppressive role in KRAS-mutant non-small-cell-lung cancer (NSCLC). In mice, tissue-specific inactivation of Stat3 resulted in increased Kras (G12D)-driven NSCLC initiation and malignant progression leading to markedly reduced survival. Clinically, low STAT3 expression levels correlate with poor survival in human lung adenocarcinoma patients with smoking history. Consistently, KRAS-mutant lung tumors showed reduced STAT3 levels. Mechanistically, we show that STAT3 controls NFÎºB-induced IL-8-expression by sequestering NFÎºB in the cytoplasm while IL-8 in turn regulates myeloid tumor infiltration and tumor vascularization thereby promoting tumor progression. These results identify a novel STAT3-NFÎºB-IL-8 axis in KRAS-mutant NSCLC with therapeutic and prognostic relevance WT: Control lung; KRAS: Lung tumors expressing KRAS G12D; KRAS STAT3 KO: Lung tumors expressing KRAS G12D- STAT3 deficient; tumors of four mice pooled per sample

2015-02-05 | E-GEOD-52798 | biostudies-arrayexpress

A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis [ATAC-Seq]

Project description:A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis [ATAC-Seq]

| PRJNA1145398 | ENA