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Fibroblast-specific reduction of heparan sulfate suppresses pancreatic cancer growth in mice

ABSTRACT: we examined how HS-reduced fibroblasts are involved in the proliferation of pancreatic cancer by using mice in which Ext-1 expression is specifically suppressed in fibroblasts.

ORGANISM(S): Mus musculus Mus

PROVIDER: GSE203598 | GEO | 2022/06/13

REPOSITORIES: GEO

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Fibroblast-specific reduction of heparan sulfate suppresses colon tumor growth in mice

Project description:we examined how HS-reduced fibroblasts are involved in the proliferation of colon cancer by using mice in which Ext-1 expression is specifically suppressed in fibroblasts.

2022-06-13 | GSE203597 | GEO

Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice

Project description:we examined how HS-reduced vascular endothelial cells are involved in the proliferation of glioma by using mice in which Ext-1 expression is specifically suppressed in vascular endothelial cells.

2021-11-17 | GSE175419 | GEO

Fibroblast-specific reduction of heparan sulfate suppresses colon tumor growth and pancreatic cancer growth in mice

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

2022-06-13 | GSE203602 | GEO

Fibroblast-specific reduction of heparan sulfate suppresses pancreatic cancer growth in mice

Project description:Fibroblast-specific reduction of heparan sulfate suppresses pancreatic cancer growth in mice

| PRJNA841564 | ENA

Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice.

Project description: Not available

| S-EPMC8585801 | biostudies-literature

TFCP2 is a transcriptional regulator of heparan sulfate assembly and melanoma cell growth

Project description:Heparan sulfate (HS) is a long, linear polysaccharide that is ubiquitously expressed in all animal cells and plays a key role in many cellular processes, including cell signaling and development. Dysregulation of HS assembly has been implicated in pathophysiological conditions, such as tumorigenesis and rare genetic disorders. HS biosynthesis occurs in a non-template driven manner in the endoplasmic reticulum and Golgi through the activity a large group of biosynthetic enzymes. While much is known about its biosynthesis, little is understood about the regulation of HS assembly across diverse tissue types and disease states. To address this gap in knowledge, we recently performed genome-wide CRISPR/Cas9 screens to identify novel regulatory factors of HS biosynthesis. From these screens, we identified the alpha globin transcription factor, TFCP2, as a top hit. To investigate the role of TFCP2 in HS assembly, we targeted TFCP2 expression in human melanoma cells using the CRISPR/Cas9 system. TFCP2 knockout cells exhibited decreased fibroblast growth factor binding to cell surface HS, alterations in HS composition, and slowed cell growth compared to wildtype cells. Additionally, RNA sequencing revealed that TFCP2 regulates expression of multiple enzymes involved in HS assembly, including the secreted endosulfatase, SULF1. Pharmacological targeting of TFCP2 activity similarly reduced growth factor binding and increased SULF1 expression, and knockdown of SULF1 expression in TFCP2 mutant cells restored melanoma cell growth. Overall, these studies identify TFCP2 as a novel transcriptional regulator of HS and highlight HS-protein interactions as a possible target to slow melanoma growth.

2023-05-01 | GSE224599 | GEO

Fibroblast-specific reduction of heparan sulfate suppresses colon tumor growth in mice

Project description:Fibroblast-specific reduction of heparan sulfate suppresses colon tumor growth in mice

| PRJNA841566 | ENA

Fibroblast-specific reduction of heparan sulfate suppresses colon tumor growth and pancreatic cancer growth in mice

Project description:Fibroblast-specific reduction of heparan sulfate suppresses colon tumor growth and pancreatic cancer growth in mice

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A genome-wide CRISPR/Cas9 screen reveals KDM2B as a modifier of protein binding to heparan sulfate

Project description:Heparan sulfate proteoglycans (HSPGs) are expressed on virtually all animal cells and are involved in many important biological processes. Each HSPG consists of a core protein with one or more covalently attached linear heparan sulfate (HS) chains composed of alternating glucosamine and uronic acids that are heterogeneously N- and O-sulfated. The arrangement and orientation of the sulfated sugar residues of HS specify the location of distinct ligand binding sites on the cell surface, and these modifications can vary temporally during development and spatially across tissues. While most of the enzymes involved in HS biosynthesis have been studied extensively, much less information exists regarding the specific mechanisms that give rise to the variable composition and binding properties of HS.

2021-01-28 | GSE163162 | GEO

A genome-wide CRISPR/Cas9 screen reveals KDM2B as a modifier of protein binding to heparan sulfate

2021-01-28 | GSE145789 | GEO

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