Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA244729 | ENA |
REPOSITORIES: ENA
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Project description:This 121-node Boolean regulatory network model that synthesizes mechanosensitive signaling that links anchorage and matrix stiffness to proliferation and migration, and cell density to contact inhibition. It can reproduce anchorage dependence and anoikis, detachment-induced cytokinesis errors, the effect of matrix stiffness on proliferation, and contact inhibition of proliferation and migration by two mechanisms that converge on the YAP transcription factor. In addition, this model offers testable predictions related to cell cycle-dependent sensitivity to anoikis, the molecular requirements for abolishing contact inhibition, substrate stiffness-dependent expression of the catalytic subunit of PI3K, heterogeneity of migratory and non-migratory phenotypes in sub-confluent monolayers, and linked inhibition but semi-independent induction of proliferation versus migration as a function of cell density and mitogenic stimulation.
The model is an extended version of the growth signaling, cell cycle and apoptosis model published in Sizek et al, PLoS Comp. Biol. 15(3): e1006402, 2019.
2020-08-26 | MODEL2006170001 | BioModels
Project description:Given previous works showing that, in the process of adipogenic differentiation of 3T3-L1 fibroblasts, the cells need to be cultured to confluency followed by additional incubation before initiating differentiation, we hypothesized that contact inhibition of proliferation (CIP) is requisite for making the cells prone to the differentiation. We screened upregulated genes in contact-inhibited 3T3-L1 fibroblasts, as well as NIH3T3 fibroblasts that are also sensitive to contact inhibition, by a whole genome microarray analysis. We also screened the genes that undergo rapid downregulation after the initiation of adipogenic differentiation. To investigate the mechanism of contact inhibition of proliferation and adipogenic differentiation of 3T3-L1 and NIH3T3 fibroblasts, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish proliferating and contact-inhibited cells and cells that undergo adipogenic differentiation. Total RNAs from 80% confluent (3T3-L1_80%, NIH3T3_80%) and overconfluent (3T3-L1_overconfluent, NIH3T3_overconfluent) cells and cells stimulated with the adipogenic differentiation medium (ZenBio) for 2 hours (3T3-L1_adipo diff med 2 hours, NIH3T3_adipo diff med 2 hours) were harvested and subjected to the microarray analysis.
2015-05-28 | E-GEOD-69320 | biostudies-arrayexpress
Project description:ING proteins play an essential role in the control of a variety of cellular functions whose deregulation is associated with tumor formation and dissemination, such as proliferation, apoptosis, senescence or invasion. Accordingly, loss of function of ING proteins is a frequent event in many types of human tumors. In this report, we have studied the function of ING4, a member of the ING family of tumor suppressors, in the context of normal, non-transformed primary fibroblasts. We show that ING4 negatively regulates cell proliferation in this cell type. The antiproliferative action of ING4 requires its ability to recognize chromatin marks, it is p53-dependent and it is lost in an ING4 cancer-associated mutant. Gene expression analysis shows that ING4 regulates the expression and release of soluble factors of the chemokine family. The secretory phenotype regulated by ING4 in primary fibroblasts displays a selective paracrine effect on proliferation, fostering the division of tumor cells, while inhibiting division in primary fibroblasts. Consistently, ING4-expressing fibroblasts promoted tumor growth in vivo in co-injection tumorigenesis assays. Collectively, our results show that ING4 not only can regulate the proliferation of primary non-transformed human fibroblasts, but also orchestrates a secretory phenotype in these cells that promotes tumor cell proliferation in vitro and in vivo. These findings support a critical role for ING4 expression in normal cells in the non-cell autonomous regulation of tumor growth. Gene expression analysis shows that ING4 regulates the expression and release of soluble factors of the chemokine family. Two independent retroviral infections were performed in early pasaje IMR-90 fibroblasts with wild-type ING4 wild type and the N214D mutant. All of them were hibridazed by duplicate againts a reference sample from vector-infected cells
2013-04-22 | E-GEOD-42412 | biostudies-arrayexpress
Project description:Given previous works showing that, in the process of adipogenic differentiation of 3T3-L1 fibroblasts, the cells need to be cultured to confluency followed by additional incubation before initiating differentiation, we hypothesized that contact inhibition of proliferation (CIP) is requisite for making the cells prone to the differentiation. We screened upregulated genes in contact-inhibited 3T3-L1 fibroblasts, as well as NIH3T3 fibroblasts that are also sensitive to contact inhibition, by a whole genome microarray analysis. We also screened the genes that undergo rapid downregulation after the initiation of adipogenic differentiation.
2015-05-28 | GSE69320 | GEO
Project description:The skin is a protective barrier against external insults and any lesion must be rapidly and efficiently repaired. Dermal fibroblasts are the major source of extracellular connective tissue matrix and play an important role in wound healing. Vitamin C is an important water-soluble free radical scavenger and an essential cofactor for collagen synthesis by dermal fibroblasts and, consequently, may contribute to the maintenance of healthy skin. Using microarray analysis, we investigated the effects of long-term exposure to a stable vitamin C derivative, ascorbic acid 2-phosphate (AA2P), in contact-inhibited populations of primary human dermal fibroblasts. Compared with "scorbutic" cells, cells exposed to AA2P increased the expression of genes associated with DNA replication and repair and with the G(2)/M phase of the cell cycle. Consistent with the gene expression changes, AA2P increased the mitogenic stimulation of quiescent fibroblasts by serum factors and cell motility in the context of wound healing. Furthermore, AA2P-treated fibroblasts showed faster repair of oxidatively damaged DNA bases. We propose that vitamin C may protect the skin by promoting fibroblast proliferation, migration, and replication-associated base excision repair of potentially mutagenic DNA lesions, and we discuss the putative involvement of hypoxia-inducible transcription factor-1 and collagen receptor-related signaling pathways.
2009-02-10 | GSE11919 | GEO
Project description:The skin is a protective barrier against external insults and any lesion must be rapidly and efficiently repaired. Dermal fibroblasts are the major source of extracellular connective tissue matrix and play an important role in wound healing. Vitamin C is an important water-soluble free radical scavenger and an essential cofactor for collagen synthesis by dermal fibroblasts and, consequently, may contribute to the maintenance of healthy skin. Using microarray analysis, we investigated the effects of long-term exposure to a stable vitamin C derivative, ascorbic acid 2-phosphate (AA2P), in contact-inhibited populations of primary human dermal fibroblasts. Compared with scorbutic cells, cells exposed to AA2P increased the expression of genes associated with DNA replication and repair and with the G(2)/M phase of the cell cycle. Consistent with the gene expression changes, AA2P increased the mitogenic stimulation of quiescent fibroblasts by serum factors and cell motility in the context of wound healing. Furthermore, AA2P-treated fibroblasts showed faster repair of oxidatively damaged DNA bases. We propose that vitamin C may protect the skin by promoting fibroblast proliferation, migration, and replication-associated base excision repair of potentially mutagenic DNA lesions, and we discuss the putative involvement of hypoxia-inducible transcription factor-1 and collagen receptor-related signaling pathways. Experiment Overall Design: Gene expression changes in response to vitamin C were analysed by Microarray technology in GM5659 human skin fibroblasts. Cells were treated with 100 µM of AA or AA2P (or growth medium alone) added fresh every day for a period of 5 days before the vitamin C-induced gene expression changes were investigated. Control, AA- and AA2P-treated samples were collected from three independent experiments each.
2009-02-21 | E-GEOD-11919 | biostudies-arrayexpress
Project description:Cancer-associated fibroblasts (CAFs) existing in tumor stroma play a crucial role in tumor progression. Here, we show that stromal fibroblasts near cancer cells are likely to display up-regulated RHBDF2 expression caused by chronic stimulation from pro-inflammatory cytokines. RHBDF2 promotes both the cleavage of type I transforming growth factor (TGF)-b receptor, through tumor necrosis factor α converting enzyme activation, and the motility of CAFs upon stimulation with TGF-b1. High-motility CAFs can consequently assist cancer cell invasion. Furthermore, the expression profiles of these cytokines are significantly associated with poor prognosis in gastric cancer (GC) patients. These findings highlight the underlying mechanism whereby cancer cells take advantage of CAFs to acquire invasiveness.
2018-08-21 | GSE83834 | GEO
Project description:ING proteins play an essential role in the control of a variety of cellular functions whose deregulation is associated with tumor formation and dissemination, such as proliferation, apoptosis, senescence or invasion. Accordingly, loss of function of ING proteins is a frequent event in many types of human tumors. In this report, we have studied the function of ING4, a member of the ING family of tumor suppressors, in the context of normal, non-transformed primary fibroblasts. We show that ING4 negatively regulates cell proliferation in this cell type. The antiproliferative action of ING4 requires its ability to recognize chromatin marks, it is p53-dependent and it is lost in an ING4 cancer-associated mutant. Gene expression analysis shows that ING4 regulates the expression and release of soluble factors of the chemokine family. The secretory phenotype regulated by ING4 in primary fibroblasts displays a selective paracrine effect on proliferation, fostering the division of tumor cells, while inhibiting division in primary fibroblasts. Consistently, ING4-expressing fibroblasts promoted tumor growth in vivo in co-injection tumorigenesis assays. Collectively, our results show that ING4 not only can regulate the proliferation of primary non-transformed human fibroblasts, but also orchestrates a secretory phenotype in these cells that promotes tumor cell proliferation in vitro and in vivo. These findings support a critical role for ING4 expression in normal cells in the non-cell autonomous regulation of tumor growth. Gene expression analysis shows that ING4 regulates the expression and release of soluble factors of the chemokine family.
2013-04-22 | GSE42412 | GEO
Project description:To investigate the differences of expression patterns in primary chicken embryo fibroblasts (CEFs) under conditions of contact-inhibition and serum starvation, we undertook a gene profiling study to characterize the transcriptomes of CEFs grown under conditions of contact inhibition, serum starvation or both, in relation to normal growing (cycling) cells.
2016-09-08 | GSE76794 | GEO
Project description:In the tumor microenvironment, Cancer Associated Fibroblasts (CAFs) become activated by cancer cells and increase their secretory activity to produce soluble factors that contribute to tumor cells proliferation, invasion and dissemination to distant organs. The pro-tumorigenic transcription factor STAT3 and its canonical inducer, the pro-inflammatory cytokine IL-6 act conjunctly in a positive feedback loop that maintains high levels of IL-6 secretion and STAT3 activation in both tumor and stromal cells. Here, we demonstrate that STAT3 is essential for the pro-tumorigenic functions of murine breast cancer CAFs both in vitro and in vivo, and identify a STAT3 signature significantly enriched for genes encoding for secreted proteins. Among those, IL-6, ANGPTL4, STC-1 and MMP13 were validated as STAT3-dependent mediators of CAF pro-tumorigenic functions by different approaches. CAFs activities were moreover impaired by IL-6 Receptor blocking antibodies and by MMP13 inhibition, supporting the feasibility of a therapeutic approach based on inhibiting STAT3-induced CAF-secreted proteins. The usefulness of such an approach is supported by the observation that an equivalent CAF-STAT3 signature in humans is expressed at high levels in breast cancer stromal cells and characterizes patients with a shorter disease specific survival, including those with basal-like disease.
2021-12-31 | GSE178081 | GEO