Normal stroma suppresses cancer cell proliferation via mechanosensitive regulation of JMJD1a-mediated transcription [RNA-Seq]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE83314 | GEO | 2016/08/29
SECONDARY ACCESSION(S): PRJNA325541
REPOSITORIES: GEO
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Project description:Tissue homeostasis is dependent on the controlled localization of specific cell types and the correct composition of the extracellular stroma. While the role of the cancer stroma in tumour progression has been well characterized, the specific contribution of the matrix itself is unknown. Furthermore, the mechanisms enabling normal-not cancer-stroma to provide tumour-suppressive signals and act as an antitumorigenic barrier are poorly understood. Here we show that extracellular matrix (ECM) generated by normal fibroblasts (NFs) is softer than the CAF matrix, and its physical and structural features regulate cancer cell proliferation. We find that normal ECM triggers downregulation and nuclear exit of the histone demethylase JMJD1a resulting in the epigenetic growth restriction of carcinoma cells. Interestingly, JMJD1a positively regulates transcription of many target genes, including YAP/TAZ (WWTR1), and therefore gene expression in a stiffness-dependent manner. Thus, normal stromal restricts cancer cell proliferation through JMJD1a-dependent modulation of gene expression.
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Project description:Matrix induced effects on gene expression in HeLa and MDA-MB-231 cells Tissue homeostasis is dependent on the spatially controlled localization of specific cell types and the correct composition of the extracellular stroma. While the role of the cancer stroma in tumor progression has been well characterized, the specific contribution of the matrix itself is unknown. Furthermore, the mechanisms enabling normal – not cancer – stroma to provide tumor suppressive signals and act as an anti-tumorigenic barrier are poorly understood. Here, we show that extracellular matrix (ECM) generated by normal fibroblasts (NFs) is softer than CAF-matrix and it is the physical and structural features of NF-generated matrix that regulate cancer cell proliferation . We find that normal stromal ECM triggers downregulation and nuclear exit of the histone demethylase JMJD1a resulting in the epigenetic growth restriction of carcinoma cells. Interestingly, JMJD1a positively regulates transcription of many target genes, including YAP/TAZ, and thus therefore gene expression in stiffness-dependent manner. Thus normal stromal restricts cancer cell proliferation through JMJD1a-dependent modulation of gene expression.
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Project description:This SuperSeries is composed of the SubSeries listed below.
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Project description:Normal stroma suppresses cancer cell proliferation via mechanosensitive regulation of JMJD1a-mediated transcription
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