Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA270547 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Mitochondrial DNA drives tumor dormancy escape in ER+ breast cancer
| PRJNA328027 | ENA
Project description:<p>BRCA1 mutations are a hallmark of hereditary ovarian cancer, strongly linked to deficiencies in homologous recombination (HR) DNA repair and impaired DNA replication fork protection. However, its roles in cancer progression beyond maintaining genomic integrity remain poorly understood. Through metabolomics approaches, we found BRCA1-deficiency strikingly increased choline metabolism. Loss of BRCA1 promotes choline uptake through upregulating choline transporter-like protein 4 (CTL4). BRCA1 directly binds and recruits EZH2-mediated H3K27Me3 deposition to CTL4 promoter. CTL4 was therefore overexpressed in ovarian cancer tissues with BRCA1 mutations. Furthermore, BRCA1-deficiency significantly promotes ovarian cancer invasion, while inhibition of CTL4 reverses the high metastatic potential of BRCA1-deficient ovarian cancer cells, suggesting the functionality and specificity of CTL4 as a therapeutic target. Additionally, we discovered that phosphocholine, the choline metabolite increased by CTL4 overexpression, interacted with and stabilized the epithelial-to-mesenchymal transition inducer FAM3C in BRCA1-deficient ovarian cancer cells. Importantly, we identified a potent CTL4 inhibitor, DT-13, which significantly reduces choline metabolism and effectively suppresses metastasis in BRCA1-deficient ovarian cancers. Therefore, our study uncovers a mechanism underlying metastasis in BRCA1-deficient cancers and identifies CTL4 as a therapeutic target for metastatic ovarian cancer patients with BRCA1 mutations.</p>
2026-05-15 | MTBLS12245 | MetaboLights
Project description:Dissemination of prostate cancer (PCa) cells to the bone marrow is an early event in the disease process. In some patients, following initial treatment, disseminated tumor cells (DTC) proliferate to form active metastases after a prolonged period of undetectable disease known as tumor dormancy. Identifying mechanisms of PCa dormancy and reactivation remain a challenge due to the lack of in vitro models. Here, we characterized in vitro PCa dormancy-reactivation by inducing three apparently dormant patient-derived xenograft (PDX) lines to proliferate through tumor cell contact with each other and with bone marrow stroma. Proliferating PCa cells demonstrated tumor cell-cell contact and integrin clustering on immunofluorescence. Global gene expression analyses on proliferating cells cultured on bone marrow stroma revealed a downregulation of TGFB2 in all of the three proliferating PCa PDX lines when compared to their non-proliferating counterparts. Furthermore, constitutive activation of myosin light chain kinase (MLCK), a downstream effector of integrin-beta1 and TGF-beta2, in non-proliferating cells resumed cell proliferation. This cell proliferation was associated with an upregulation of CDK6 and a downregulation of E2F4. Taken together, our data provide evidence to support cellular adhesion and downregulation of TGFB2 as a potential mechanism by which PCa cells escape from dormancy. Targeting TGF-beta 2-associated mechanism could provide novel opportunities to prevent lethal PCa metastasis. Custom Agilent-016162 44K whole human genome expression oligonucleotide microarrays were used to profile dormant and proliferating cells isolated from three separate LuCaP xenograft lines grown in co-culture with bone marrow stromal cells isolated from a patient with PCa bone metastases. RNA from 10 cells was amplified prior to hybridization against a common reference pool of prostate tumor cell lines.
2015-10-26 | E-GEOD-64262 | biostudies-arrayexpress
Project description:Tumor Cell Heterogeneity and Dormancy in Single Disseminated Prostate Cancer Cells
| PRJNA212632 | ENA
Project description:Dissemination of prostate cancer (PCa) cells to the bone marrow is an early event in the disease process. In some patients, following initial treatment, disseminated tumor cells (DTC) proliferate to form active metastases after a prolonged period of undetectable disease known as tumor dormancy. Identifying mechanisms of PCa dormancy and reactivation remain a challenge due to the lack of in vitro models. Here, we characterized in vitro PCa dormancy-reactivation by inducing three apparently dormant patient-derived xenograft (PDX) lines to proliferate through tumor cell contact with each other and with bone marrow stroma. Proliferating PCa cells demonstrated tumor cell-cell contact and integrin clustering on immunofluorescence. Global gene expression analyses on proliferating cells cultured on bone marrow stroma revealed a downregulation of TGFB2 in all of the three proliferating PCa PDX lines when compared to their non-proliferating counterparts. Furthermore, constitutive activation of myosin light chain kinase (MLCK), a downstream effector of integrin-beta1 and TGF-beta2, in non-proliferating cells resumed cell proliferation. This cell proliferation was associated with an upregulation of CDK6 and a downregulation of E2F4. Taken together, our data provide evidence to support cellular adhesion and downregulation of TGFB2 as a potential mechanism by which PCa cells escape from dormancy. Targeting TGF-beta 2-associated mechanism could provide novel opportunities to prevent lethal PCa metastasis.
2015-10-26 | GSE64262 | GEO
Project description:The paper describes a basic model of immune-induced cancer dormancy and immune evasion.
Created by COPASI 4.25 (Build 207)
This model is described in the article:
Mathematical models of immune-induced cancer dormancy and the emergence of immune evasion
Kathleen P. Wilkie and Philip Hahnfeldt
Interface Focus 3: 20130010
Abstract:
Cancer dormancy, a state in which cancer cells persist in a host without sig- nificant growth, is a natural forestallment of progression to manifest disease and is thus of great clinical interest. Experimental work in mice suggests that in immune-induced dormancy, the longer a cancer remains dormant in a host, the more resistant the cancer cells become to cytotoxic T-cell-mediated killing. In this work, mathematical models are used to analyse the possible causative mechanisms of cancer escape from immune-induced dormancy. Using a data-driven approach, both decaying efficacy in immune predation and immune recruitment are analysed with results suggesting that decline in recruitment is a stronger determinant of escape than increased resistance to predation. Using a mechanistic approach, the existence of an immune- resistant cancer cell subpopulation is considered, and the effects on cancer dormancy and potential immunoediting mechanisms of cancer escape are analysed and discussed. The immunoediting mechanism assumes that the immune system selectively prunes the cancer of immune-sensitive cells, which is shown to cause an initially heterogeneous population to become a more homogeneous, and more resistant, population. The fact that this selec- tion may result in the appearance of decreasing efficacy in T-cell cytotoxic effect with time in dormancy is also demonstrated. This work suggests that through actions that temporarily delay cancer growth through the targeted removal of immune-sensitive subpopulations, the immune response may actually progress the cancer to a more aggressive state.
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.
2024-09-02 | BIOMD0000000751 | BioModels
Project description:The paper describes a model of immune-induced cancer dormancy and immune evasion with resistance.
Created by COPASI 4.25 (Build 207)
This model is described in the article:
Mathematical models of immune-induced cancer dormancy and the emergence of immune evasion
Kathleen P. Wilkie and Philip Hahnfeldt
Interface Focus 3: 20130010
Abstract:
Cancer dormancy, a state in which cancer cells persist in a host without sig- nificant growth, is a natural forestallment of progression to manifest disease and is thus of great clinical interest. Experimental work in mice suggests that in immune-induced dormancy, the longer a cancer remains dormant in a host, the more resistant the cancer cells become to cytotoxic T-cell-mediated killing. In this work, mathematical models are used to analyse the possible causative mechanisms of cancer escape from immune-induced dormancy. Using a data-driven approach, both decaying efficacy in immune predation and immune recruitment are analysed with results suggesting that decline in recruitment is a stronger determinant of escape than increased resistance to predation. Using a mechanistic approach, the existence of an immune- resistant cancer cell subpopulation is considered, and the effects on cancer dormancy and potential immunoediting mechanisms of cancer escape are analysed and discussed. The immunoediting mechanism assumes that the immune system selectively prunes the cancer of immune-sensitive cells, which is shown to cause an initially heterogeneous population to become a more homogeneous, and more resistant, population. The fact that this selec- tion may result in the appearance of decreasing efficacy in T-cell cytotoxic effect with time in dormancy is also demonstrated. This work suggests that through actions that temporarily delay cancer growth through the targeted removal of immune-sensitive subpopulations, the immune response may actually progress the cancer to a more aggressive state.
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.
2024-09-02 | BIOMD0000000752 | BioModels
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
2010-09-25 | GSE24338 | GEO
Project description: Not available
| S-EPMC2531291 | biostudies-literature
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO