Gene expression of KP4 and A549 cells regulated by matrix stiffness and ATF5
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PROVIDER: PRJNA1061192 | ENA |
REPOSITORIES: ENA
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Project description:Cancer tissues are stiffer than normal tissues. Carcinogenesis stiffens the extracellular matrix (ECM) of cancerous tissues, to which cancer cells respond by activating transcription factors. We show that activating transcription factor 5 (ATF5), highly expressed in tumors, is activated by ECM stiffness and promotes the proliferation of cancer cells, including that of pancreatic cancer cells (KP4) and lung cancer cells (A549). In addition, ATF5 suppressed the expression of early growth response 1 (EGR1), thereby accelerating cancer cell proliferation. Stiff ECMs trigger the JAK-MYC pathway which activates ATF5.
2025-03-06 | GSE252565 | GEO
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
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 | GSE250066 | 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: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
Project description:We have found that the expression pattern of Atf5 is highly restricted to the olfactory system, strongly suggesting that Atf5 is an olfactory sensory neuron-specific transcription factor. To test this possiblity, we compared gene expression profiles in olfactory epithelium (septa and turbinates) from Atf5+/+ and Atf5-/- mice. Olfactory septa and turbinates were dissected from Atf5+/+ and Atf5-/- P0 pups from different litters (n=3 for each genotype) and pooled into a single sample. Three independent samples were prepared for each genotype.
2012-10-30 | E-GEOD-37609 | biostudies-arrayexpress
Project description:We have found that the expression pattern of Atf5 is highly restricted to the olfactory system, strongly suggesting that Atf5 is an olfactory sensory neuron-specific transcription factor. To test this possiblity, we compared gene expression profiles in olfactory epithelium (septa and turbinates) from Atf5+/+ and Atf5-/- mice.
2012-10-30 | GSE37609 | GEO
Project description:Extracellular matrix proteomic profiling Mass spectrometry characterization illustrated a reprogrammed proteome in response to matrix stiffness, including a core subset of 84 ECM-specific proteins, including various ECM regulators and tissue-associated ECM-related proteins. Further, we observe remodeling of ECM proteome with softer substrates associated with metabolic/mitochondrial network (178 proteins), while with 40 kPa substrate (92 proteins enriched) resulting in networks associated with enrichment of collagen biosynthesis, integrin cell surface interactions, and extracellular matrix organization networks.
| MSV000092971 | MassIVE
Project description:Nrf2 regulated genes in A549 cells
| PRJNA451429 | ENA