Response to TGFB in colon fibroblasts
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE64192 | GEO | 2015/01/28
SECONDARY ACCESSION(S): PRJNA270356
REPOSITORIES: GEO
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Project description:We obtained gene expression signatures from TGF-beta treated fribroblasts. Upregulated genes predict poor prognosis in Colorectal Cancer. Fibroblasts extracted from human normal colon mucosa were treated with TGF-β1 for 8 hours. Gene expression profiles for treated or untreated fibroblasts were measured in duplicate using HG-133+PM Affimetrix arrays.
2015-01-28 | E-GEOD-64192 | biostudies-arrayexpress
Project description:Mouse tumour organoids (MTOs) derived from a compound mutant (LAKTP) intestinal cancer model were orthoptopically transplanted into syngeneic C57BL/6J mice. Tumour-bearing mice were treated with TGF-beta inhibitor Galunisertib or vehicle control. Whole tumour mRNA was extracted from primary tumours and expression profiling was performed with the objective to characterize the tumour microenvironment (TME). As a TGF-beta-activated TME has been associated to a poor prognosis and the CRC consensum molecular subtype CMS4, and the mouse model was found to have such an activated TME, we used the array data to classify these tumours in this mouse model system as CMS4-like. Furthermore, treatment with TGF-beta inhibitor reduced the fibroblast- and T cell-specific TGF-beta response signatures, also associated to poor prognosis in human CRC. This treatment was associated to a strong reduction/prevention of liver metastasis, as well as a reduction of primary tumour (and local carcinomatosis) size.
2018-02-12 | GSE103562 | GEO
Project description:RATIONALE: Measuring levels of transforming growth factor-beta (TGF-beta) in the blood of patients with epithelial cancers (head and neck, lung, breast, colorectal, and prostate) may help doctors predict how patients will respond to treatment with radiation therapy.
PURPOSE: This research study is measuring levels of TGF-beta in patients with epithelial cancers who are undergoing radiation therapy.
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Project description:To recognize the influnence of WNT signaling on fibroblasts differentiation first we analyzed transformation of human cardiac fibroblasts caused by TGF-β signaling. Differential gene expression analysis demonstrated that cardiac fibroblasts 72h after treatment with TGF-β showed deregulated expression of 313 genes. We also observed that stimulation with WNT3a resulted in deregulation of 124 genes in TGF-β-treated fibroblasts and in contrast to profound effect of WNT3a on fibroblasts differentiation, treatment with WNT5a upregulated expression of only 2 and downregulated 21 genes in TGF-β-activated cells.
2021-08-08 | GSE181575 | GEO
Project description:The survival of isolated metastatic cells and expansion into macroscopic tumour has been recognized as a limiting step for metastasis formation in several cancer types yet the determinants of this process remain largely uncharacterized. In colorectal cancer (CRC), we identify a transcriptional programme in tumour-associated stromal cells, which is intimately linked to a high risk of developing recurrent disease after therapy. A large proportion of CRCs display mutational inactivation of the TGF-beta pathway but paradoxically they are characterized by high TGF-beta production. In these tumours, TGF-beta instructs a transcriptional programme in stromal cells, which confers a high risk of developing metastatic disease. We quantified the association of TGF-beta-activated fibroblasts with disease progression. To this end, we used as surrogates the gene expression programme upregulated by addition of TGF-beta to normal colon mucosa-derived fibroblasts (CCD-Co-18) in culture. CCD-Co-18 were seeded at 60% confluence and treated with TGF-β1. Gene expression profiles were measured in duplicate using HG-U133 plus 2.0. We used RMA background correction, quantile normalization and RMA summarization (Gautier et al., 2004). A TGF-β response signature was obtained by selecting genes with limma P-value < 0.05 and at least two fold up-regulation in TGF-β treated fibroblasts.
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Project description:Phenotypic plasticity is a major driver of cancer progression, metastasis, and treatment resistance. However, the principles governing human cancer plasticity associated with poor prognosis remain poorly understood due to the lack of in vitro models. Here we identified a unique cancer cell state at single-cell resolution to predict poor prognosis across several human cancers with different clinical features, especially colorectal cancer (CRC) progression and metastasis, named the poor prognostic plastic state (PPPS). A functional patient-derived organoid xenograft (PDOX) model was developed to capture and maintain the PPPS in CRC. With a marker gene of MSLN (encoding mesothelin), this model was used to validate the role of the PPPS in promoting CRC metastasis. Moreover, precise manipulation of human cancer plasticity through the PPPS allows us to identify small-molecule inhibitors of non-canonical IKKs to promote malignancy, with clinical implications for targeting the PPPS to prevent CRC progression and metastasis.
2024-04-17 | GSE261004 | GEO
Project description:Transforming growth factor-β (TGF-β) signaling and microRNAs (miRNAs) are important gene regulatory components in cancer. Usually in advanced malignant stages, TGF-β signaling is elevated, but global miRNA expression is suppressed. Such a gene expression signature is well illustrated in a fibrosis/mesenchymal subtype of ovarian cancer (OC) that is of poor prognosis. However, the interplay between the two pathways in the OC subtype has not yet been elucidated. nc886 is a recently identified non-coding RNA implicated in several malignancies. nc886's high expression is associated with the poor prognosis of 285 patients in an OC cohort. Herein we have found in OC that nc886 expression is induced by TGF-β and that nc886 binds to the enzyme Dicer to inhibit the processing of miRNA precursors into mature forms. By preventing the miRNA pathway, nc886 emulates TGF-β in gene expression patterns and potentiates cell adhesion, migration, invasion, and drug resistance. We report nc886 as a novel molecular link between the TGF-β and miRNA pathways.
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Project description:Constitutive Wnt activation upon loss of Adenoma polyposis coli (APC) acts as main driver of colorectal cancers (CRC). Targeting Wnt signaling has proven difficult because the pathway is crucial for homeostasis and stem cell renewal. To distinguish oncogenic from physiologic Wnt activity, we have performed transcriptome and proteome profiling in isogenic human colon organoids. Culture in the presence or absence of exogenous ligand allowed us to discriminate receptor-mediated signaling from the effects of CRISPR/Cas9 induced APC loss. We could catalogue two non-overlapping molecular signatures that were stable at distinct levels of stimulation. Newly identified markers for normal stem/progenitor cells and adenomas were validated by immunohistochemistry and flow cytometry. We found that oncogenic Wnt signals are associated with good prognosis in tumors of the consensus molecular subtype 2 (CMS2). In contrast, receptor-mediated signaling was linked to CMS4 tumors and poor prognosis. Together, our data represent a valuable resource for biomarkers that allow more precise stratification of Wnt responses in CRC.
2019-02-28 | PXD012650 | Pride
Project description:The survival of isolated metastatic cells and expansion into macroscopic tumour has been recognized as a limiting step for metastasis formation in several cancer types yet the determinants of this process remain largely uncharacterized. In colorectal cancer (CRC), we identify a transcriptional programme in tumour-associated stromal cells, which is intimately linked to a high risk of developing recurrent disease after therapy. A large proportion of CRCs display mutational inactivation of the TGF-beta pathway but paradoxically they are characterized by high TGF-beta production. In these tumours, TGF-beta instructs a transcriptional programme in stromal cells, which confers a high risk of developing metastatic disease. We quantified the association of TGF-beta-activated fibroblasts with disease progression. To this end, we used as surrogates the gene expression programme upregulated by addition of TGF-beta to normal colon mucosa-derived fibroblasts (CCD-Co-18) in culture.
2013-01-17 | GSE39394 | GEO
Project description:The role of TGF-β-induced epithelial-mesenchymal transition (EMT) in cancer cell dissemination is well established, but the involvement of lncRNAs in TGF-β signaling is still unknown. In this study, we observed that the lncRNA-Activated by TGF-β (lncRNA-ATB) was upregulated in hepatocellular carcinoma (HCC) metastases and associated with poor prognosis. lncRNA-ATB promotes the invasion-metastasis cascade, which suggest that lncRNA-ATB, a mediator of TGF-β signaling, could predispose HCC patients to metastases and may serve as a potential target for anti-metastatic therapies.
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