Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

An in vivo systematic genetic analysis of tumour progression in Drosophila identifies the cohesin complex as an invasion suppressor

ABSTRACT: Metastasis is the leading cause of death for cancer patients. Consequently it is imperative that we improve our understanding of the molecular mechanisms that underlie progression of tumour growth towards malignancy. Advances in genome characterisation technologies have been very successful in identifying commonly mutated or misregulated genes in a variety of human cancers. However the difficulty in evaluating whether these candidate genes drive tumour progression remains a major challenge. Using the genetic amenability of Drosophila melanogaster we generated tumours with specific genotypes in the living animal and carried out a detailed systematic loss-of-function analysis to identify conserved genes that enhance or suppress epithelial tumour progression. This enabled the discovery of functional cooperative regulators of invasion and the establishment of a network of conserved invasion suppressors. This includes constituents of the cohesin complex, which can either promote individual or collective invasion, depending on the severity of effect on cohesin function. We used Clariom™ S Assay arrays to detail the global programme of gene expression following STAG2 KD to detect DEG involved in regulation of cell motility and cell-cell junction assembly and maintenance.

ORGANISM(S): Homo sapiens

PROVIDER: GSE137773 | GEO | 2020/06/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

CG7379/ING1 in cancer progression. A study of migration and invasion in in vivo and in vitro epithelial systems

Project description:Metastasis is the leading cause of death for cancer patients. Consequently it is imperative that we improve our understanding of the molecular mechanisms that underlie progression of tumour growth towards malignancy. A large-scale genetic screen was carried out to identify genes that affect tumour progression in the living fly. This screen identified CG7379 as promoting cancer cell invasion when gene expression was knocked down in epithelial tumours in the dorsal thorax of the fly. The uncharacterised CG7379 Drosophila gene shows high homology with the human ING (inhibitor of growth) gene family. ING proteins are known to be involved in the control of cell proliferation, senescence and apoptosis. However, their potential role in cell migration and invasion is yet to be properly documented. Homeostasis of epithelial tissues relies on the control of cell polarity and architecture, and our results strongly suggest that CG7379 and ING1 play an important role in cell-cell junction integrity maintenance. The knockdown of both the Drosophila and human gene increases invasion in the living animal and in in vitro invasion assays respectively and gene knock-down led to severe disruption of cell-cell junction integrity. We used Clariom™ S Assay arrays to detail the global programme of gene expression following ING1 KD to detect DEG involved in regulation of cell motility and cell-cell junction assembly and maintenance.

2021-09-22 | GSE125438 | GEO

Gene expression profiling of control cohesin knockdown LSK cells

Project description:We performed RNA-sequencing in LSK cells (Lin(neg)/c-Kit(+)/Sca-1(+)) from shRNA mice carrying an shRNA for Renilla, Smc1a or Stag2. RNA-sequencing control (Renilla) and cohesin (Smc1a and Stag2) knockdown cells.

2015-09-16 | E-GEOD-72369 | biostudies-arrayexpress

Truncating mutations of STAG2 define a molecular subgroup of aneuploid bladder cancers with poor prognosis.

Project description:Aneuploidy is among the most common hallmarks of cancer, yet the underlying genetic mechanisms are still poorly defined. We have recently identified STAG2 as a gene that is mutated in human cancer and whose inactivation leads directly to chromosomal instability and aneuploidy. However, no single tumor type has yet been identified in which inactivation of a cohesin subunit represents a predominant mutational event. Here we used immunohistochemistry to screen a panel of 2,214 tumors from each of the major human tumor types to identify additional tumor types harboring somatic loss of STAG2. Strikingly, STAG2 expression was completely absent in 18% of urothelial carcinomas, the most common type of bladder cancer and the fifth most common cancer in the United States. DNA sequencing revealed that somatic mutations of STAG2 were present in 21% of urothelial carcinomas, which were found to be a group of highly aneuploid tumors. The acquisition of STAG2 mutations was shown to be an early event in the pathogenesis of urothelial carcinoma. STAG2 loss was significantly associated with lymph node invasion, increased disease recurrence, and reduced cancer-specific survival. These results identify STAG2 as one of the most commonly mutated genes in bladder cancer discovered to date, and demonstrate that STAG2 inactivation defines an aggressive subtype of bladder cancer with particularly poor prognosis. Affymetrix CytoScan HD Arrays were performed according to the manufacturer's directions on genomic DNA extracted directly from snap-frozen human urothelial carcinoma primary tumors. Copy number analysis using Affymetrix CytoScan HD Arrays was performed for 12 human urothelial carcinomas of the bladder with truncating mutations of the STAG2 gene.

2013-06-30 | E-GEOD-41581 | biostudies-arrayexpress

A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis

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. 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.

2024-10-22 | GSE277290 | GEO

ea1b5928-f11a-4df1-9290-6aba4b1cf95e - samples

Project description:ChIP-Seq targeting the cohesin subunit STAG2 in STAG2-mutant or cohesin wildtype adult AMLs.

| EGAD00001011205 | EGA

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]

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 | GSE274204 | GEO

STAG2 promotes the myelination transcriptional program in oligodendrocytes [Hi-C]

Project description:Cohesin folds chromosomes via DNA loop extrusion. Cohesin-mediated chromosome loops regulate transcription by shaping long-range enhancer-promoter interactions, among other mechanisms. Mutations of cohesin subunits and regulators cause human developmental diseases termed cohesinopathy. Vertebrate cohesin consists of SMC1, SMC3, RAD21, and either STAG1 or STAG2. To probe the physiological functions of cohesin, we created conditional knockout (cKO) mice with Stag2 deleted in the nervous system. Stag2 cKO mice exhibit growth retardation, neurological defects, and premature death, in part due to insufficient myelination of nerve fibers. Stag2 cKO oligodendrocytes exhibit delayed maturation and downregulation of myelinationrelated genes. Stag2 loss reduces promoter-anchored loops at downregulated genes in oligodendrocytes. Thus, STAG2-cohesin generates promoter-anchored loops at myelinationpromoting genes to facilitate their transcription. Our study implicates defective myelination as a contributing factor to cohesinopathy and establishes oligodendrocytes as a relevant cell type to explore the mechanisms by which cohesin regulates transcription.

2022-08-23 | GSE186893 | GEO

STAG2 promotes the myelination transcriptional program in oligodendrocytes [scRNA-seq]

2022-08-23 | GSE186892 | GEO

STAG2 promotes the myelination transcriptional program in oligodendrocytes [ChIP-seq]

2022-08-23 | GSE186891 | GEO