Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA343100 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To elucidate the mechanisms underlying the enhanced sensitivity to arginine in the absence of ASS1 expression in endometrial cancer cells, we performed DNA microarray-based gene expression profiling using HEC1B harboring the empty vector (EV) and ASS1-knockout (KO) HEC1B cells. Since accumulating evidence has shown that arginine regulates mTORC1 activity, we focused on the expression patterns of genes related to the mTOR complex. ASS1-KO HEC1B cells had lower DEPTOR transcript abundance than EV cells, while no significant difference was observed in the expression levels of genes coding for other mTOR complex components such as mTOR, RAPTOR, or RICTOR. Indeed, immunoblot analysis confirmed that the expression level of DEPTOR protein was significantly decreased in ASS1-KO HEC1B cells, which were cultured in arginine-replete conditions.
2017-04-02 | GSE86963 | GEO
Project description:Micro-RNAs expressed in oligometastases inhibit genes involved with adhesion, invasion and motility
| PRJNA259511 | ENA
Project description:Depleting the microenvironment of important nutrients such as arginine is a key strategy for immune evasion by cancer cells. Many tumors overexpress arginase but it is unclear how these cancers, but not T-cells, tolerate arginine depletion. Here, we show that tumor cells synthesize arginine from citrulline by upregulating argininosuccinate synthetase 1 (ASS1). Under arginine starvation, ASS1 transcription is induced by ATF4 and CEBPbeta binding to a previously uncharacterized enhancer within ASS1. T-cells cannot induce ASS1, despite the presence of active ATF4 and CEBPbeta, as the gene is repressed. Arginine starvation drives global chromatin compaction and repressive histone methylation which disrupts ATF4/CEBPbeta binding and target gene transcription. We find that T-cell activation is impaired in arginine-depleted conditions, with significant metabolic perturbation linked to incomplete chromatin remodeling and misregulation of key genes. Our results highlight a T-cell behavior mediated by nutritional stress, exploited by cancer cells to enable pathological immune evasion.
2021-05-10 | GSE137033 | GEO
Project description:Depleting the microenvironment of important nutrients such as arginine is a key strategy for immune evasion by cancer cells. Many tumors overexpress arginase but it is unclear how these cancers, but not T-cells, tolerate arginine depletion. Here, we show that tumor cells synthesize arginine from citrulline by upregulating argininosuccinate synthetase 1 (ASS1). Under arginine starvation, ASS1 transcription is induced by ATF4 and CEBPbeta binding to a previously uncharacterized enhancer within ASS1. T-cells cannot induce ASS1, despite the presence of active ATF4 and CEBPbeta, as the gene is repressed. Arginine starvation drives global chromatin compaction and repressive histone methylation which disrupts ATF4/CEBPbeta binding and target gene transcription. We find that T-cell activation is impaired in arginine-depleted conditions, with significant metabolic perturbation linked to incomplete chromatin remodeling and misregulation of key genes. Our results highlight a T-cell behavior mediated by nutritional stress, exploited by cancer cells to enable pathological immune evasion.
2021-05-10 | GSE137032 | GEO
Project description:Depleting the microenvironment of important nutrients such as arginine is a key strategy for immune evasion by cancer cells. Many tumors overexpress arginase but it is unclear how these cancers, but not T-cells, tolerate arginine depletion. Here, we show that tumor cells synthesize arginine from citrulline by upregulating argininosuccinate synthetase 1 (ASS1). Under arginine starvation, ASS1 transcription is induced by ATF4 and CEBPbeta binding to a previously uncharacterized enhancer within ASS1. T-cells cannot induce ASS1, despite the presence of active ATF4 and CEBPbeta, as the gene is repressed. Arginine starvation drives global chromatin compaction and repressive histone methylation which disrupts ATF4/CEBPbeta binding and target gene transcription. We find that T-cell activation is impaired in arginine-depleted conditions, with significant metabolic perturbation linked to incomplete chromatin remodeling and misregulation of key genes. Our results highlight a T-cell behavior mediated by nutritional stress, exploited by cancer cells to enable pathological immune evasion.
2021-05-10 | GSE137031 | GEO
Project description:Cen3tel cells, obtained by telomerase immortalization of human fibroblasts, gradually underwent neoplastic transformation and became metastatic in immunocompromised mice. Neoplastic transformation was associated with a change in cell morphology (from fibroblastic to polygonal). Tumorigenic cells acquired a clear-cut membrane localization of adhesion molecules, a reorganization of the actin cytoskeleton, increased cell motility and invasiveness. In a 3-dimensional environment, tumorigenic cells showed a spherical morphology with cortical actin rings, suggesting a switch from a mesenchymal to an amoeboid ROCK-dependent movement. Accordingly, cell invasion decreased upon treatment with the ROCK inhibitor Y27632, but not with the matrix protease inhibitor Ro28-2653. The increased invasiveness of tumorigenic cen3tel cells was associated with a reduced expression of RhoE, a cellular inhibitor of ROCK. Ectopic RhoE expression decreased cen3tel invasion capability. These results point to RhoE and ROCK as regulators of invasiveness of mesenchymal tumor cells and indicate ROCK as a possible therapeutic target.
2011-04-20 | GSE15742 | GEO
Project description:Cen3tel cells, obtained by telomerase immortalization of human fibroblasts, gradually underwent neoplastic transformation and became metastatic in immunocompromised mice. Neoplastic transformation was associated with a change in cell morphology (from fibroblastic to polygonal). Tumorigenic cells acquired a clear-cut membrane localization of adhesion molecules, a reorganization of the actin cytoskeleton, increased cell motility and invasiveness. In a 3-dimensional environment, tumorigenic cells showed a spherical morphology with cortical actin rings, suggesting a switch from a mesenchymal to an amoeboid ROCK-dependent movement. Accordingly, cell invasion decreased upon treatment with the ROCK inhibitor Y27632, but not with the matrix protease inhibitor Ro28-2653. The increased invasiveness of tumorigenic cen3tel cells was associated with a reduced expression of RhoE, a cellular inhibitor of ROCK. Ectopic RhoE expression decreased cen3tel invasion capability. These results point to RhoE and ROCK as regulators of invasiveness of mesenchymal tumor cells and indicate ROCK as a possible therapeutic target. The cen3tel telomerase immortalized cell line was obtained from primary cen3 fibroblasts, derived from a centenarian individual, by infection with an hTERT-containing retrovirus (Mondello et al., 2003). Cen3tel cells were used at different steps of propagation, reflecting different phases of transformation (Zongaro et al., 2005) to study variations in the migratory and invasive potential accompanying human fibroblast neoplastic transformation. Raw data files: *NORM.txt test is Cy5 and *DS.txt test is Cy3.
2011-04-20 | E-GEOD-15742 | biostudies-arrayexpress
Project description:The response of primary human endothelial (ECs) and vascular smooth muscle cells (VSMCs) to TiO2 nanotube arrays is studied through gene expression analysis. Microarrays revealed that nanotubes enhanced EC proliferation and motility, decreased VSMC proliferation, and decreased expression of molecules involved in inflammation and coagulation in both cell types. Network generated from significantly affected genes suggests that cells may be sensing nanotopographical cues via pathways previously implicated in sensing shear stress.
2010-08-14 | GSE17676 | GEO
Project description:the genetic inactivation of Khk-C enhanced the survival of KPC-driven PDAC model even in absence of high fructose diet. Moreover Khk-C knock out decreased the viability of KPC organoids and cancer cells, the migratory capability of PDAC cells in vitro and the growth of KPC cells in vivo in a cell autonomous manner.
2023-07-07 | E-MTAB-12746 | biostudies-arrayexpress
Project description:Although ADSL is an enzyme that is involved in de novo purine synthesis, it was reported that ADSL knockdown did not result in decreases in adenine nucleotides (AMP, ADP, and ATP) or GTP. Then, we hypothesized that decreased cell proliferation, migration and invasion capability by ADSL knockdown in endometrial cancer cells were caused through a mechanism independent of purine synthesis. To elucidate a mechanism, we performed DNA microarray-based gene expression profiling using ADSL knockdown and control HEC1B cells. In the analysis, 940 out of 34,127 probes showed greater than two-fold changes in expression with a significant difference, p value < 0.05.
2018-03-08 | GSE100703 | GEO