Non-programmed dissemination of cancer cell clusters induce malignant properties through Integrin beta 1 activation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA725950 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14352231_1.fastq.gz | Fastqsanger.gz | |||
| SRR14352231_2.fastq.gz | Fastqsanger.gz | |||
| SRR14352232_1.fastq.gz | Fastqsanger.gz | |||
| SRR14352232_2.fastq.gz | Fastqsanger.gz | |||
| SRR14352233_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:We found that epithelial cluster recruiment soluble fibronectin and then activating beta1 Integrin induce epithelial-mesenchymal transition and enhance cancer cells’ malignant after cell dissemination. Non-programmed dissemination of cluster cells triggers ERK cascade and then accelerate tumor growth and metastasis. Our finding reveals that cell cluster plays a vital role in the non-programmed dissemination of breast cancer cells’ metastasis, offering a potential new therapeutic target for metastasis patients.
2022-12-31 | GSE173538 | GEO
Project description:Cancer metastasis requires the transient activation of cellular programs enabling dissemination and seeding in distant organs. Genetic, transcriptional and translational heterogeneity contributes to this dynamic process. Metabolic heterogeneity has also been observed, yet its role for cancer progression is less explored. Here, we discover that loss of phosphoglycerate dehydrogenase (PHGDH) potentiates metastatic dissemination. Specifically, we find that heterogeneous or low PHGDH expression in primary tumors of breast cancer patients is associated with decreased metastasis free survival time. In mice, circulating tumor cells and early metastatic lesions are enriched with PHGDH low cancer cells and silencing PHGDH in primary tumors increases metastasis formation. Mechanistically, PHGDH protein interacts with the glycolytic enzyme phosphofructokinase (PFK) and the loss of this interaction activates the hexosamine – sialic acid pathway, which provides precursors for protein glycosylation. Consequently, aberrant protein glycosylation including increased sialylation of integrin αvβ3 occurs, which potentiates cell migration and invasion. Inhibition of sialic acid metabolism counteracts the metastatic capacity of PHGDH low cancer cells. In conclusion, while the catalytic activity of PHGDH supports cancer cell proliferation, low PHGDH protein expression non-catalytically potentiates cancer dissemination and metastasis formation. Thus, the presence of PHDGH heterogeneity in primary tumors may be considered a sign of tumor aggressiveness.
2022-03-30 | GSE198380 | GEO
Project description:We have found that thyroid hormones (THs), acting as soluble integrin αvβ3 ligands, activate growth-related signaling pathways in T-cell lymphomas (TCL). Specifically, TH-activated αvβ3 integrin signaling promotes TCL proliferation and angiogenesis, in part, via the up-regulation of VEGF.
2015-02-18 | GSE63122 | GEO
Project description:We have found that thyroid hormones (THs), acting as soluble integrin αvβ3 ligands, activate growth-related signaling pathways in T-cell lymphomas (TCL). Specifically, TH-activated αvβ3 integrin signaling promotes TCL proliferation and angiogenesis, in part, via the up-regulation of VEGF. CUTLL1 cells were treated with T3- and T4-bound agarose or agarose alone for 24hrs. Total RNA was harvested from cells and used for expression profiling via RNA-seq.
2015-02-18 | E-GEOD-63122 | biostudies-arrayexpress
Project description:Geier2011 - Integrin activation
Rule based model that integrates the available data to test the biololical hypotheses regarding the role of talin, Dok1 and PIPKI in integrin activation.
This model is described in the article:
A computational analysis of the dynamic roles of talin, Dok1, and PIPKI for integrin activation.
Geier F, Fengos G, Iber D.
PLoS One. 2011;6(11):e24808.
Abstract:
Integrin signaling regulates cell migration and plays a pivotal role in developmental processes and cancer metastasis. Integrin signaling has been studied extensively and much data is available on pathway components and interactions. Yet the data is fragmented and an integrated model is missing. We use a rule-based modeling approach to integrate available data and test biological hypotheses regarding the role of talin, Dok1 and PIPKI in integrin activation. The detailed biochemical characterization of integrin signaling provides us with measured values for most of the kinetics parameters. However, measurements are not fully accurate and the cellular concentrations of signaling proteins are largely unknown and expected to vary substantially across different cellular conditions. By sampling model behaviors over the physiologically realistic parameter range we find that the model exhibits only two different qualitative behaviors and these depend mainly on the relative protein concentrations, which offers a powerful point of control to the cell. Our study highlights the necessity to characterize model behavior not for a single parameter optimum, but to identify parameter sets that characterize different signaling modes.
This model is hosted on BioModels Database
and identified
by: MODEL1208280001
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2014-03-05 | MODEL1208280001 | BioModels
Project description:Integrins provide an essential bridge between cancer cells and the extracellular matrix, playing a central role in every stage of disease progression. Despite the recognized significance of integrin phosphorylation in several biological processes, the regulatory mechanisms and their relevance remained elusive. To address this gap, we engineered a fluorescence resonance energy transfer biosensor for integrin β1 phosphorylation, screening 96 protein tyrosine phosphatases and identifying Shp2 and PTP-PEST as negative regulators. Mutation of the integrin NPxY(783/795) sites revealed the importance of integrin phosphorylation for efficient cancer cell invasion, further supported by inhibition of the identified integrin phosphorylation regulators Shp2 and Src kinase. Using proteomics approaches, we uncovered Cofilin as a component of the phosphorylated integrin-Dok1 complex and linked this axis to effective invadopodia formation, a process supporting breast cancer invasion. These data further implicate dynamic modulation of integrin β1 phosphorylation at NPxY sites at different stages of metastatic dissemination.
2025-02-05 | PXD048646 | Pride
Project description:Multiple myeloma (MM) is a plasma cell malignancy characterized by the presence of multiple foci in the skeleton. These distinct tumor foci indicate cycles of tumor growth and dissemination that seed new clusters and drives disease progression. Utilizing an intra-tibial Vk*MYC murine myeloma, we found that CD169 + radiation-resistant, tissue-resident macrophages (MPs) were critical for myeloma early dissemination and disease progression. While depletion of these MPs had no effect on tumor proliferation, it reduced myeloma BM egress and spreading to other bones, which improved overall survival as a single therapy and in combination with BM transplantation. Myeloma dissemination correlated with an increased inflammatory signature in BM MPs, as well as production of IL-6 and TNFα by tumor-associated MPs (TAMs). Exogenous i.v. IL-6 and TNFa could trigger myeloma intravasation in the BM by increasing vascular leakiness in the BM, and by enhancing myeloma motility by reducing CD138 adhesion. Moreover, mice lacking IL-6 had defects in myeloma dissemination as in MP-depleted recipients. While in TNFa or TNFaR deficient mice had defects in MM dissemination, engraftment was also impaired. These effects on myeloma dissemination required production of cytokines in the radiation-resistant compartment, containing these radiation-resistant BM MPs. Taken together, we propose BM egress of myeloma cells is regulated by localized inflammation in foci, driven in part by CD169 + MPs.
2021-06-09 | GSE176385 | GEO
Project description:The NALCN channel regulates metastasis and non-malignant cell dissemination
| PRJNA863884 | ENA
Project description:programmed ribosomal frameshift Raw sequence reads
| PRJNA310019 | ENA
Project description:This dataset contains proximity-labeling mass spectrometry measurements generated to investigate how loss of bata4-integrin affects nuclear integrity, nuclear mechanics, lamin composition, and nuclear pore complex (NPC) organization in prostate epithelial cells.
2025-12-08 | MSV000100146 | MassIVE