Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1146728 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Interactions with the extracellular matrix (ECM) through integrin adhesion receptors provide cancer cells with physical and chemical cues that act in concert with growth factors to support survival and proliferation. Preclinical studies testing beta1 integrin antagonists in (breast) cancer models have shown inhibition of tumor growth and sensitization to radio- or chemotherapy and these strategies are currently evaluated in clinical trials. Here, we show that disruption of beta1 integrin-mediated ECM adhesion attenuates breast tumor growth but dissemination to the lungs from such small tumors can be markedly enhanced. beta1 integrin downregulation induces compensatory upregulation of beta3 integrins, but increased beta3 expression does not lead to enhanced lung metastasis. Instead, beta1 integrin downregulation in human and mouse triple negative, E-cadherin positive breast cancer cells elicits a switch from collective invasion to individual cell migration in 3D ECM. This involves alterations in the TGFbeta-BMP signaling network shifting the balance between miR-200 and ZEB, which causes a block in E-cadherin transcription. The switch is fully reversible: restored beta1 expression reinstates E-cadherin expression and cell cohesion. Moreover, restoring the network at the level of TGFbetaR, ZEB/miR-200 balance, or E-cadherin, restores cohesion and prevents the induction of lung metastasis without affecting tumor growth. These findings reveal that integrin-mediated ECM-attachments regulate a signaling network in control of epithelial characteristics that suppress metastatic spread. This raises concerns with respect to the use of beta1 integrins as cancer drug targets
2014-02-11 | E-MTAB-2185 | biostudies-arrayexpress
Project description:Vascular smooth muscle cells require beta1 integrin for survival. Following the induced deletion of smooth muscle beta1 integrin, smooth muscle cells undergo apoptosis and arteries become fibrotic. This microarray study on mesenteric arteries 2 weeks after the initiation of beta1 integrin deletion specifically in smooth muscle cells of the adult mouse aimed to examine early changes in expression following deletion.
2013-02-26 | GSE44663 | GEO
Project description:Vascular smooth muscle cells require beta1 integrin for survival. Following the induced deletion of smooth muscle beta1 integrin, smooth muscle cells undergo apoptosis and arteries become fibrotic. This microarray study on mesenteric arteries 2 weeks after the initiation of beta1 integrin deletion specifically in smooth muscle cells of the adult mouse aimed to examine early changes in expression following deletion. Mesenteric arteries from three wild type mixed background and three beta1 integrin smooth muscle knockout mixed background mice are examined.
2013-02-26 | E-GEOD-44663 | biostudies-arrayexpress
Project description:The goal of the study was to understand how integrin beta1 expressed in epithelial cells directs developmental angiogenesis. Integrin beta1 was deleted specifically in the pituitary glands of embryonic mice. RNA was isolated from knockout and WT control pituitaries dissected at e12.5, one day prior to the initiation of developmental angiogenesis.
2016-10-26 | GSE89171 | GEO
Project description:The formation of healthy tissue involves continuous remodelling of the extracellular matrix (ECM). Whilst it is known that this requires integrin-associated cell-ECM adhesion sites (CMAs) and actomyosin-mediated forces, the underlying mechanisms remain unclear. Here we examine how tensin3 contributes to formation of fibrillar adhesions (FBs) and fibronectin fibrillogenesis. Using BioID mass spectrometry and a mitochondrial targeting assay, we establish that tensin3 associates with the mechanosensors talin and vinculin. We show that the talin R11 rod domain binds directly to a helical motif within the central intrinsically disordered region (IDR) of tensin3, whilst vinculin binds indirectly to tensin3 via talin. Using CRISPR knock-out cells in combination with defined tensin3 mutations, we show (i) that tensin3 is critical for formation of alpha5 beta1-integrin FBs and for fibronectin fibrillogenesis, and (ii) the talin/tensin3 interaction drives this process, with vinculin acting to potentiate it.
2022-09-09 | PXD026343 | Pride
Project description:Ligand-independent integrin beta1 signaling supports lung adenocarcinoma development
| PRJNA733190 | ENA
Project description:CRISPR screen data
2023-05-31 | E-MTAB-12929 | biostudies-arrayexpress
Project description:Synthetic lethal CRISPR screen in MCF10A FBXW7 isogenic models
2023-05-22 | E-MTAB-12939 | biostudies-arrayexpress