Normal stroma suppresses cancer cell proliferation via mechanosensitive regulation of JMJD1a-mediated transcription
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE83370 | GEO | 2016/08/29
SECONDARY ACCESSION(S): PRJNA325721
REPOSITORIES: GEO
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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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