Impact of ECM Stiffness on Breast Cancer Dormancy in BC-M1 Cells
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PROVIDER: PRJEB89750 | ENA |
REPOSITORIES: ENA
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Project description:ECM Stiffness and Breast Cancer Dormancy
| PRJEB89749 | ENA
Project description:The Rho family GTPases, Rac and Rho, play critical roles in transmitting mechanical information contained within the extracellular matrix (ECM) to the cell. Rac and Rho have well described roles in regulating stiffness-dependent actin remodeling, proliferation and motility. However, much less is known about the relative roles of these GTPases in stiffness-dependent transcription, particularly at the genome-wide level. Here, we selectively inhibited Rac and Rho in mouse embryonic fibroblasts cultured on deformable substrata and used RNA sequencing to elucidate and compare the contribution of these GTPases to the early transcriptional response to ECM stiffness. Surprisingly, we found that the stiffness-dependent activation of Rac is dominant over Rho in the initial transcriptional response to ECM stiffness. We also identified Activating Transcription Factor 3 (ATF3) as a major target of stiffness/Rac-mediated signaling and show that ATF3 repression by ECM stiffness helps to explain how the stiffness-dependent activation of Rac results in the induction of cyclin D1.
2023-10-04 | GSE236266 | GEO
Project description:We report the expression profiles of MCF10A cells encapsulated in hydrogels of varying stiffness and composition. Cells were encapsulated for 7 days in either 1.) soft alginate and reconstituted basement membrane (rBM), 2.) stiff alginate and rBM, 3,) soft col-1 and rBM, or 4.) stiff col-1. We find global gene expression changes in response to enhanced ECM stiffness, independent of expression changes in response to col-1 exposure. These results provide a comprehensive study of the gene expression changes associated with increased ECM stiffness in addition to the gene expression changes associated with increased col-1 concentration in combination with, and independent of, ECM stiffness.
2019-03-25 | GSE102506 | GEO
Project description:Cell dormancy is a major factor leading to drug resistance as well as the high rate of late recurrence and mortality in estrogen receptor-positive (ER+) breast cancer. Although some studies have highlighted the significant impact of the microenvironment on dormant cells, they have largely overlooked the mechanical forces stemming from the stiffness of the surrounding extracellular matrix. Previously, we demonstrated that soft matrix promotes tumor cell proliferation and migration, while stiff matrix induces tumor cell dormancy and drug resistance. In this study, we present a comprehensive analysis of the proteome and phosphoproteome in response to gradient changes in matrix stiffness, elucidating the mechanisms behind cell dormancy induced drug resistance. Overall, we found that membrane transport and anti-apoptotic processes may be mainly involved in mechanical force induced dormancy resistance of ER+ breast cancer cells.
2024-09-11 | PXD046799 |
Project description:Almost all cells respond to the mechanical stiffness of their microenvironment through alter gene expression. Mammary epithelial cells respond to the mechanics of the extracellular matrix (ECM) in a way that can alter their behaviour and be pro-oncogenic. How increased ECM stiffness promotes transformation is unclear, but it can increase the incidence of DNA damage. This experiment was undertaken to identify changes in gene expression in non-tumorigenic mammary epithelial cells (murine Eph4) in response to different ECM stiffness. Epg4 cells were grown in either a soft or stiff 3D Matrigel-Alginate hydrogel, or on soft and stiff 2D polyacrylamide hydrogel. RNAseq was undertaken to identify gene expression changes associated with both stiffness and 2D vs. 3D culture conditions.
2025-10-22 | E-MTAB-15122 | biostudies-arrayexpress
Project description:Extracellular matrix (ECM) stiffness plays a crucial role in regulating cell fate and maturation, but its influence on lung development is limited known. Here we utilized stiffness-tunable gelatin methacryloyl (GelMA) hydrogels to investigate how ECM stiffness influences site-specific lung development in a stem cell-derived lung organoid model. We found increased stiffness promoted NKX2-1+ lung progenitor cells (LPCs) generation. In airway organoids (hAWOs), stiff hydrogels directed proximal airway differentiation enriched with goblet, ciliated, and basal cells; whereas the decreased stiffness favored emergence of secretory cells in the proximal-distal transition zone and distal airway. In alveolar organoids (hALOs), increased stiffness enhanced AT2 and AT1 cells transition. Moreover, infection assays with Omicron BA.1.1 and Delta variants recapitulated the proximal-to-distal tropism of SARS-CoV-2 in the lung. Transcriptomic sequencing revealed ECM stiffness regulates lung development via Hippo, TGF-β, HIF and Wnt pathways. These findings advance mechanism understanding of ECM stiffness on lung development and provide a novel mechanical regulation for generating site-specific lung organoids.
2026-06-02 | GSE292932 | GEO
Project description:Extracellular matrix (ECM) stiffness plays a crucial role in regulating cell fate and maturation, but its influence on lung development is limited known. Here we utilized stiffness-tunable gelatin methacryloyl (GelMA) hydrogels to investigate how ECM stiffness influences site-specific lung development in a stem cell-derived lung organoid model. We found increased stiffness promoted NKX2-1+ lung progenitor cells (LPCs) generation. In airway organoids (hAWOs), stiff hydrogels directed proximal airway differentiation enriched with goblet, ciliated, and basal cells; whereas the decreased stiffness favored emergence of secretory cells in the proximal-distal transition zone and distal airway. In alveolar organoids (hALOs), increased stiffness enhanced AT2 and AT1 cells transition. Moreover, infection assays with Omicron BA.1.1 and Delta variants recapitulated the proximal-to-distal tropism of SARS-CoV-2 in the lung. Transcriptomic sequencing revealed ECM stiffness regulates lung development via Hippo, TGF-β, HIF and Wnt pathways. These findings advance mechanism understanding of ECM stiffness on lung development and provide a novel mechanical regulation for generating site-specific lung organoids.
2026-06-02 | GSE293170 | GEO
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
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 | GSE272027 | GEO
Project description:Vascular extracellular matrix (ECM) stiffening is a risk factor for aortic and coronary artery disease. How matrix stiffening regulates the transcriptome profile of human aortic (Ao) and coronary (Co) vascular smooth muscle cells (VSMCs) is not well understood. Furthermore, the role of long non-coding RNAs (lncRNAs) in the cellular response to stiffening has never been explored. This study characterizes the stiffness-sensitive transcriptome of human Ao and Co VSMCs and identify potentially key lncRNA regulators of stiffness-dependent VSMC functions. Ao and Co VSMCs were cultured on hydrogel substrates mimicking physiologic and pathologic ECM stiffness. Total RNA-seq was performed to compare the stiffness-sensitive transcriptome profiles of Ao and Co VSMCs.
2017-12-01 | GSE100081 | GEO