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Matrix stiffness modulates androgen response genes and chromatin state in prostate cancer (RNA-seq)

ABSTRACT: Matrix stiffness modulates androgen response genes and chromatin state in prostate cancer (RNA-seq)

PROVIDER: PRJNA1134738 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29779619.fastq.gz	Fastqsanger.gz
	SRR29779620.fastq.gz	Fastqsanger.gz
	SRR29779621.fastq.gz	Fastqsanger.gz
	SRR29779622.fastq.gz	Fastqsanger.gz
	SRR29779623.fastq.gz	Fastqsanger.gz

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Matrix stiffness modulates androgen response genes and chromatin state in prostate cancer (RNA-seq)

Project description:The interplay between the extracellular matrix (ECM) and prostate cancer (PCa) tumor has been shown to increase ECM stiffness, correlating with more aggressive disease forms. However, the impact of ECM stiffness on the androgen receptor (AR), a primary PCa treatment target, remains elusive. Here, we aimed to explore whether matrix stiffness influences PCa progression, transcriptional regulation, chromatin state, and AR function in AR-positive PCa cells under varying ECM stiffness conditions. We utilized ATAC-seq and RNAseq in different ECM conditions and the SUC2 metastatic prostate adenocarcinoma patient dataset to understand the role of ECM stiffness on chromatin state, androgen response genes and to evaluate the effect of matrix stiffness on prostate cancer progression. Results showed that increased ECM stiffness elevated the expression of genes related to proliferation and differentiation. In contrast, androgen response genes were most induced in soft ECM conditions. Combining chromatin accessibility with transcriptomic results revealed that androgen response genes were more transcriptionally available in soft ECM conditions. Additionally, increased ECM stiffness upregulated genes associated with low overall survival in the SUC2 dataset. Taken together, our results indicate that high expression of hard matrix stiffness genes potentially promotes prostate cancer progression leading to more aggressive forms of the disease with poor survival rate.

2025-03-06 | GSE272028 | GEO

Matrix stiffness modulates androgen response genes and chromatin state in prostate cancer (ATAC-seq)

2025-03-06 | GSE272027 | GEO

Matrix stiffness modulates androgen response genes and chromatin state in prostate cancer

Project description:Matrix stiffness modulates androgen response genes and chromatin state in prostate cancer

| PRJNA1134682 | ENA

Matrix stiffness modulates androgen response genes and chromatin state in prostate cancer (ATAC-seq)

Project description:Matrix stiffness modulates androgen response genes and chromatin state in prostate cancer (ATAC-seq)

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Biphasic Regulation of Epigenetic State by Matrix Stiffness during Cell Reprogramming [RNA-seq]

Project description:In this study, we investigate how matrix stiffness regulates chromatin reorganization and cell reprogramming, and find that matrix stiffness acts as a biphasic regulator of epigenetic state and fibroblast-to-neuron conversion efficiency, maximized at an intermediate stiffness of 20 kPa. ATAC-sequencing analysis shows the same trend of chromatin accessibility to neuronal genes at these stiffness levels. Concurrently, we observe peak levels of histone acetylation and histone acetyltransferase (HAT) activity in the nucleus on matrices at 20 kPa, and inhibiting HAT activity abolishes matrix stiffness effects. G-actin and cofilin, the co-transporters shuttling HAT into the nucleus, rises with decreasing matrix stiffness; however, reduced importin-9 on soft matrices limits nuclear transport. These two factors result in a biphasic regulation of HAT transport into the nucleus, which is directly demonstrated on matrices with dynamically tunable stiffness. These findings unravel a mechanism of the mechano-epigenetic regulation that is valuable for cell engineering in disease modeling and regenerative medicine applications.

2023-12-19 | GSE250068 | GEO

Biphasic Regulation of Epigenetic State by Matrix Stiffness during Cell Reprogramming [ATAC-seq]

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Three-Dimensional Matrix Stiffness Modulates Mechanosensitive and Phenotypic Alterations in Oral Squamous Cell Carcinoma Spheroids

Project description:Extracellular biophysical cues such as matrix stiffness are key stimuli tuning cell fate and affecting tumor progression in vivo. However, it remains unclear how spheroids in a 3D microenvironment perceive matrix mechanical stiffness stimuli and translate them into intracellular signals driving cancer. Mechanosensitive Piezo1 and TRPV4 ion channels, upregulated in many malignancies, are major transducers of such physical stimuli into biochemical responses. Most mechanotransduction studies probing the reception of changing stiffness cues by cells are, however, still limited to 2D culture systems or cell-extracellular matrix models which lack the major cell-cell interactions prevalent in 3D cancer tumors. Here, we engineered a 3D spheroid culture environment with varying mechanobiological properties to study the effect of static matrix stiffness stimuli on mechanosensitive and malignant phenotypes in oral squamous cell carcinoma spheroids. We find that spheroid growth is enhanced when cultured in stiff extracellular matrix. Using flow cytometry, we show that the expression of mechanoreceptor Piezo1 and stemness marker CD44 is upregulated in stiff matrix. We also report the upregulation of a selection of genes with associations to mechanoreception, ion channel transport, extracellular matrix organization, and tumorigenic phenotypes in stiff matrix spheroids. Together, our results indicate that cancer cells in 3D spheroids utilize mechanosensitive ion channels Piezo1 and TRPV4 to sense changes in static extracellular matrix stiffness and that stiffness drives pro-tumorigenic phenotypes in oral squamous cell carcinoma.

2024-03-28 | GSE262142 | GEO

Matrix stiffness modulates androgen response genes and chromatin state in prostate cancer

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

2025-03-06 | GSE272029 | GEO

Matrix stiffness modulates fibrogenesis in hepatic stellate cells through AP-1-induced chromatin priming

Project description:Matrix stiffness modulates fibrogenesis in hepatic stellate cells through AP-1-induced chromatin priming

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Three-Dimensional Matrix Stiffness Modulates Mechanosensitive and Phenotypic Alterations in Oral Squamous Cell Carcinoma Spheroids

Project description:Three-Dimensional Matrix Stiffness Modulates Mechanosensitive and Phenotypic Alterations in Oral Squamous Cell Carcinoma Spheroids

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