Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA270059 | ENA |
REPOSITORIES: ENA
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Project description:The transcription factor nuclear factor-κB (NF-κB) has important roles for tumorigenesis, but how it regulates cancer stem cells (CSCs) remains largely unclear. We identified insulin-like growth factor 2 (IGF2) is a key target of NF-κB activated by HER2/HER3 signaling to form tumor spheres in breast cancer cells. The IGF2 receptor, IGF1 R, was expressed at high levels in CSC-enriched populations in primary breast cancer cells. Moreover, IGF2-PI3K (IGF2-phosphatidyl inositol 3 kinase) signaling induced expression of a stemness transcription factor, inhibitor of DNA-binding 1 (ID1), and IGF2 itself. ID1 knockdown greatly reduced IGF2 expression, and tumor sphere formation. Finally, treatment with anti-IGF1/2 antibodies blocked tumorigenesis derived from the IGF1Rhigh CSC-enriched population in a patient-derived xenograft model. Thus, NF-κB may trigger IGF2-ID1-IGF2-positive feedback circuits that allow cancer stem-like cells to appear. Then, they may become addicted to the circuits. As the circuits are the Achilles' heels of CSCs, it will be critical to break them for eradication of CSCs.
2016-09-05 | GSE64073 | GEO
Project description:miR363-3p Mediates Maintenance and Chemoresistance of Breast Cancer Stem Cells
| PRJNA362190 | ENA
Project description:Cyclin D1 is a well characterised cell cycle regulator with established oncogenic capabilities. Despite these properties, studies report contrasting links to tumour aggressiveness. It has previously been shown that silencing cyclin D1 increases the migratory capacity of MDA-MB-231 breast cancer cells with concomitant increase in ‘inhibitor of differentiation 1’ (ID1) gene expression. Id1 is known to be associated with more invasive features of cancer and with the epithelial-mesenchymal transition (EMT). Here, we sought to determine if the increase in cell motility following cyclin D1 silencing was mediated by Id1 and enhanced EMT-features. To further substantiate these findings we aimed to delineate the link between CCND1, ID1 and EMT, as well as clinical properties in primary breast cancer. The increase in cell migration following cyclin D1 silencing in MDA-MB-231 cells was abolished by Id1 siRNA treatment and we observed cyclin D1 occupancy of the Id1 promoter region. Moreover, ID1 and SNAI2 gene expression was increased following cyclin D1 knock-down, an effect reversed with Id1 siRNA treatment. Similar migratory and SNAI2 increases were noted for the ER-positive ZR75-1 cell line, but in an Id1 independent manner. In a meta-analysis of 1107 breast cancer samples, CCND1 and ID1 gene expression were associated with mesenchymal-markers including SNAI1, SNAI2 and TWIST1, and with clinicopathological parameters. Finally, a greater percentage of CCND1low/ID1high tumours were found in the EMT-like ‘claudin-low’ subtype of breast cancer than in other subtypes. Together, these results indicate that increased migration of MDA-MB-231 cells following cyclin D1 silencing can be mediated by Id1 and is linked to an increase in EMT markers. Moreover, we have confirmed a relationship between cyclin D1, Id1 and EMT in primary breast cancer, supporting our in vitro findings that low cyclin D1 expression can be linked to aggressive features in subgroups of breast cancer. MDA-MB-231 cells were transfected with cyclin D1, CDK4/6 or control siRNA.
2011-10-12 | E-GEOD-27260 | biostudies-arrayexpress
Project description:Id1 and its closely related family member Id3 are expressed by a diversity of stem and progenitor cells. We show that Id1/3 are required for the self-renewal and proliferation of triple negative breast cancer (TNBC) cells both in vitro and in vivo. Furthermore, we identified that Id1/3 negatively regulates the tumour suppressor gene Robo1. Depletion of Robo1 could rescue the proliferative defect induced by Id1/3 knockdown. To understand the mechanisms by which Robo1 rescues cell proliferation in Id1/3 depleted cells, we performed RNA-Sequencing on 4T1 cells with Dox-inducible Id1/3 KD and/or Robo1 depletion using siRNA. We conclude that following Id1/3 knockdown, Robo1 is induced and exerts anti-proliferative effects via suppression of a Myc transcriptional program.
2020-10-31 | GSE129858 | GEO
Project description:Metastasis is a major factor responsible for mortality in breast cancer patients. Id1 plays important roles in cell differentiation and promotes tumor angiogenesis, cell invasion and metastasis. Although Id1 is established as a critical factor for lung metastasis in breast cancer, the pathways and molecular mechanisms of Id1 functions in metastasis remains to be defined. Here we show that Id1 interacts with TFAP2A to suppress S100A9 expression. The expression of Id1 and S100A9 is inversely correlated in both breast cancer cell lines and clinical samples. We also find that S100A9 expression rescues the migratory and invasive phenotypes in vitro and metastasis in vivo induced by Id1 expression. S100A9 also suppresses the expression of known metastasis promoting factor RhoC activated by Id1 expression. Our results suggest that S100A9 mediates the functions of Id1 in breast cancer metastasis.
2017-08-29 | GSE53847 | GEO
Project description:Cyclin D1 is a well characterised cell cycle regulator with established oncogenic capabilities. Despite these properties, studies report contrasting links to tumour aggressiveness. It has previously been shown that silencing cyclin D1 increases the migratory capacity of MDA-MB-231 breast cancer cells with concomitant increase in ‘inhibitor of differentiation 1’ (ID1) gene expression. Id1 is known to be associated with more invasive features of cancer and with the epithelial-mesenchymal transition (EMT). Here, we sought to determine if the increase in cell motility following cyclin D1 silencing was mediated by Id1 and enhanced EMT-features. To further substantiate these findings we aimed to delineate the link between CCND1, ID1 and EMT, as well as clinical properties in primary breast cancer. The increase in cell migration following cyclin D1 silencing in MDA-MB-231 cells was abolished by Id1 siRNA treatment and we observed cyclin D1 occupancy of the Id1 promoter region. Moreover, ID1 and SNAI2 gene expression was increased following cyclin D1 knock-down, an effect reversed with Id1 siRNA treatment. Similar migratory and SNAI2 increases were noted for the ER-positive ZR75-1 cell line, but in an Id1 independent manner. In a meta-analysis of 1107 breast cancer samples, CCND1 and ID1 gene expression were associated with mesenchymal-markers including SNAI1, SNAI2 and TWIST1, and with clinicopathological parameters. Finally, a greater percentage of CCND1low/ID1high tumours were found in the EMT-like ‘claudin-low’ subtype of breast cancer than in other subtypes. Together, these results indicate that increased migration of MDA-MB-231 cells following cyclin D1 silencing can be mediated by Id1 and is linked to an increase in EMT markers. Moreover, we have confirmed a relationship between cyclin D1, Id1 and EMT in primary breast cancer, supporting our in vitro findings that low cyclin D1 expression can be linked to aggressive features in subgroups of breast cancer.
2011-10-13 | GSE27260 | GEO
Project description:Abnormal activation of stemness factors is a crucial signature of cancer stem cells (CSCs), a highly tumorigenic subpopulation in malignant tumors. However, it is unclear whether multi-signaling pathways are activated in CSCs, as like normal stem cells. I would like to report that an inhibitor of differentiation 1 (ID1) activates intracellular multi-signaling involved in proliferation, genesis, and maintenance of glioma stem cells (GSCs) by suppression of Cullin3, an E3 ubiquitin ligase that degrades Cyclin E and components of SHH and WNT signaling. ID1 inhibits BMP-dependent differentiation of GSCs by activation of BMPR2-targeting miR17/20a. ID1HIGH-Cullin3LOW signature correlates with a poor prognosis of GBM patients with a significant association to gene signatures enriched in EGF, WNT, SHH, and BMP signaling. Combinational inhibition of GSC intracellular multi-signaling network increases tumor-bearing mice survival. These results provide insights on molecular and cellular basis of GSC biology, and also suggest necessity of multi-signaling inhibition for GSCs therapy. Two human primary glioma stem cells (GSCs) such as GSC2 and GSC8 were isolated from two individual primary human glioma specimens. The GSCs were directly transfected with pSuper-GFP-ID1-shRNA and pSuper-GFP-Scrambled-shRNA using FuGENE 6 reagent (Roche). The RNA extraction in these cells was used to analyze gene expression.
2013-09-05 | E-GEOD-40614 | biostudies-arrayexpress
Project description:Id1 knockdown in primary human glioma stem cells
| PRJNA177719 | ENA
Project description:Understanding the mechanism by which embryonic stem (ES) cells self-renew is critical for the realization of their therapeutic potential. Previously it had been shown that in combination with LIF, Id proteins were sufficient to maintain mouse ES cells in a self-renewing state. Here we investigate the requirement for Id1 in maintaing ES cell self-renewal and blocking differentiation. We find that Id1-/- ES cells have a propensity to differentiate and a decreased capacity to self-renew. Chronic or acute loss of Id1 leads to a down-regulation of Nanog, a critical regulator of self-renewal. In addition, in the absence of Id1, ES cells express elevated levels of Brachyury, a marker of mesendoderm differentiation. We find that loss of both Nanog and Id1 is required for the up-regulation of Brachyury, and Id1 maintains Nanog expression by blocking the expression of Zeb1, a repressor of Nanog transcription. These results identify Id1 as an important factor in the maintenance of ES cell self-renewal and suggest a plausible mechanism for its control of lineage commitment. Wild type and Id1-/- ES cells were grown on gelatin under normal self-renewing conditions (in the presence of serum and LIF).
2011-11-01 | E-GEOD-19144 | biostudies-arrayexpress