Mechanical cues control mutant p53 stability through a Mevalonate/RhoA axis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE93529 | GEO | 2017/12/23
SECONDARY ACCESSION(S): PRJNA361002
REPOSITORIES: GEO
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2023-04-18 | GSE229742 | GEO
Project description:Almost all solid tumors become stiff with progression of cancer. Cancer Associated Fibroblasts (CAFs), most abundant stromal cells in the tumor microenvironment (TME), are known to mediate the stiffening. While the biochemical crosstalk between CAFs and cancer cells have been widely investigated, it is yet not clear whether CAFs in stiffer TME promote metastatic progression, and if so, how. To address this question, here we explore the role of mechanical stiffness and cell traction force in regulating human colorectal CAF (CAF05 cell line) gene expressions that are relevant to metastatic progression. We cultured CAFs on 2D polyacrylamide hydrogels with increasing elastic modulus (E) of 1, 10 and 40 kPa, and quantified corresponding cell spreading area and cytoskeletal force. We performed genome-wide transcriptome analyses in these cells to identify differentially expressed genes on 40 KPa compared to those on 1 kPa substrate. The latter represents normal tissue stiffness of colon.
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Project description:Purpose: Mechanical homeostasis is a crucial process for endothelial cell (EC) survival and functionality. Cells can sense environmental change and modify the expression of extracellular matrix, focal adhesion and cytoskeleton protein to maintain the correct mechanical homeostasis. In this study, we observed change in mRNA levels linked with mechanical response. ECs were seeded for 48 hour on PDMS 3 kPa and 30 kPa substrate coating with fibronectin to simulate "soft" and "stiff" substrate, then RNA-seq was performed.
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Project description:Purpose: Mechanical homeostasis is a crucial process for endothelial cell (EC) survival and functionality. Cells can sense environmental change and modify the expression of extracellular matrix, focal adhesion and cytoskeleton protein to maintain the correct mechanical homeostasis. In this study, we observed change in microRNA levels linked with mechanical response. ECs were seeded for 48 hour on PDMS 3 kPa and 30 kPa substrate coating with fibronectin to simulate "soft" and "stiff" substrate, then sRNA-seq was performed.
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Project description:Purpose: mechanical homeostasis is a crucial process for Humen dermal fibroblast cell (HDFs) survival and functionality. Cell can sense environmental change and modify the expression of extracellular matrix, focal adhesion and cytoskeleton protein to maintain the correct mechanical homeostasis. In this study we observed change in microRNA levels linked with mechanical response. HDFs were seeded for 48 our on PDMS 3 kPa and 30 kPa substrate coating with fibronectin to simulate "soft" and "stiff" substrate, then sRNA-seq was performed.
2019-03-31 | GSE123008 | GEO
Project description: Not available
| S-EPMC6179142 | biostudies-literature
Project description:We undertook mRNA microarray and gene ontology analyses to screen out substrate stiffness-dependent genes. Total mRNA were extracted from E17 cortical neurons grown on soft or stiff substrates at 5 or 16 hr time points. We identified 114 differentially-expressed mRNA transcripts in cells grown on 0.1 kPa and 20 kPa gels at the 5 hr time-point. Among them, 66 were upregulated in 0.1 kPa gel cultures and the remainder were downregulated (compared to cells grown on stiffer substrates). The expressions of three endocytic genes (Cltc, Dab2, and Myo6) and four adhesion genes(Vcl, Robo2, Nrcam, and Cad11) were confirmed by QGP and smRNA FISH.
2018-01-08 | GSE102350 | GEO
Project description:Purpose: When we infect MDCK epithelial cells we low dosage of Listeria monocytogenes, we observe that at late times (24 h) post-infection the infected cells pertaining in infection foci get collectively extruded out of the epithelial monolayer forming a 3D mound. The formation of the infection mound results from the competition between two populations: the uninfected cells ("surrounders") that eventually squeeze and extrude the infected cells ("mounders") in the infected wells. The extracellular matrix where the host cells adhere appears to impact the formation of infection mounds with more mounding on glassr as opposed to soft 3 kPa substrata, as evidenced by confocal 3D microscopy. Here we built poalyacrylamide hydrogels of varing stiffness (3 kPa soft or 70 kPa stiff) and coated them with collagen I rat tail. We also placed host cells on glass collagen I-coated surfaces. We then infected for 24 h (or not) the host cells with Listeria monocytogenes to infer how matrix stiffness-dependent gene expression of MDCK cells in monolayers changes in uninfected versus infected wells, through RNA-Sequencing. Our goal was to understand how matrix stiffness impacts transcriptional regulation of host cells and whether that could modulate the collective extrusion of infected epithelial cells triggered by surrounding uninfected cells. Methods and Results: By analyzing the differentially expressed genes between all conditions we find a significant number of up- or down-regulated genes between all groups, other than between cells residing on soft versus stiff polyacrylamide hydrogels that behave similarly in terms of gene expression. Through pathway enrichement analysis, we find that cells residing on polyacrylamide hydrogels as opposed to cells residing on glass show higher upregulation of a number of innate immune signaling related pathways (e.g. MAPK, TNF) even when infection is not involved. When comparing infected versus not wells, the relative differences in gene expression for cells residing on glass are higher than for cells residing on hydrogels. However certain specific innate immune signaling pathways that regulate mound formation (https://www.sciencedirect.com/science/article/abs/pii/S1534580721000708), show higher upregulation in infection for cells on hydrogels as opposed to glass (e.g. IL-17, TNF, NF-κΒ; evidenced by pathway enrichement analysis). Finally, through pathway enrichement analysis we find that the relative change based on enrichement score when comparing uninfected versus infected settings for cells residing on glass versus on polyacrylamide hydrogels is lower for the former (i.e. for cells residing on glass) for NF-κB, TNF and IL17. However, with regards to the MAPK pathway the enrichment score of cells from infected versus uninfected wells, is much higher for cells residing on glass as opposed to polyacrylamide hydrogles. Conclusions: Infection of MDCK epithelial cells with Listeria monocytogenes significantly alters the transcriptome of the infected host cells when those are examined 24 h post infection and compared to uninfected cells on all different substrata. Compared to cells residing on glass substrates cells residing on polyacrylamide hydrogels (irrespective of whether the stiffness is low i.e. 3 kPa or high i.e. 70 kPa) show significant differences both when uninfected settings and when infected ones are compared.
2021-09-01 | GSE175784 | GEO