E-MTAB-7451
Ontology highlight
ABSTRACT:
PROVIDER: E-MTAB-7451 | ExpressionAtlas | 2021-01-19
REPOSITORIES: ExpressionAtlas
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Project description:Dis3L2 regulates cell proliferation and tissue growth through a conserved mechanism
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Project description:Protein Kinase C alpha (PKC) is a critical mediator of cell signaling and cancer growth. We show that PKC inhibitors decrease proliferation in squamous cell carcinoma of the head and neck (SCCHN) cells and abrogate growth of SCCHN tumors in mouse xenografts. Analysis of gene expression arrays reveals that PKC regulates cell cycle genes required for DNA synthesis. In particular, PKC increases cyclin E protein expression, cyclinE/cdk2 complex formation, and transcription of cyclin E and E2F target genes. Consistent with this mechanism, expression of cyclin E rescues the block in DNA synthesis caused by PKC inhibition. In SCCHN tissue, PKC and cyclin E expression increase progressively from normal and dysplastic to malignant human head and neck tissue. Furthermore, PKCÂ expression correlates with poor prognosis in SCCHN. These results demonstrate that PKC regulates growth by stimulating DNA synthesis through cyclin E and E2F and identify PKC as a therapeutic target that is highly expressed in aggressive SCCHN. Experiment Overall Design: 9 samples composed of treated replicates at three time points
2009-03-28 | E-GEOD-10299 | biostudies-arrayexpress
Project description:Background—YAP, the nuclear effector of Hippo signaling, regulates cellular growth and survival in multiple organs, including the heart, by interacting with TEAD sequence specific DNA-binding proteins. Recent studies showed that YAP stimulates cardiomyocyte proliferation and survival. However, the direct transcriptional targets through which YAP exerts its effects are poorly defined. Methods and Results—To identify genes directly regulated by YAP in cardiomyocytes, we combined differential gene expression analysis in YAP gain- and loss-of-function with genome-wide identification of YAP bound loci using chromatin immunoprecipitation and high throughput sequencing. This screen identified Pik3cb, encoding p110β, a catalytic subunit of phosphoinositol-3-kinase (PI3K), as a candidate YAP effector that promotes cardiomyocyte proliferation and survival. We validated YAP and TEAD occupancy of a conserved enhancer within the first intron of Pik3cb, and show that this enhancer drives YAP-dependent reporter gene expression. Yap gain- and loss-of-function studies indicated that YAP is necessary and sufficient to activate the PI3K-Akt pathway. Like Yap, Pik3cb gain-of-function stimulated cardiomyocyte proliferation, and Pik3cb knockdown dampened the YAP mitogenic activity. Reciprocally, Yap loss-of-function impaired heart function and reduced cardiomyocyte proliferation and survival, all of which were significantly rescued by AAV-mediated Pik3cb expression. Conclusion—Pik3cb is a crucial direct target of YAP, through which the YAP activates PI3K-AKT pathway and regulates cardiomyocyte proliferation and survival. Yap wild type ChIPseq and input
2015-02-20 | E-GEOD-57717 | biostudies-arrayexpress
Project description:Protein Kinase C alpha (PKC) is a critical mediator of cell signaling and cancer growth. We show that PKC inhibitors decrease proliferation in squamous cell carcinoma of the head and neck (SCCHN) cells and abrogate growth of SCCHN tumors in mouse xenografts. Analysis of gene expression arrays reveals that PKC regulates cell cycle genes required for DNA synthesis. In particular, PKC increases cyclin E protein expression, cyclinE/cdk2 complex formation, and transcription of cyclin E and E2F target genes. Consistent with this mechanism, expression of cyclin E rescues the block in DNA synthesis caused by PKC inhibition. In SCCHN tissue, PKC and cyclin E expression increase progressively from normal and dysplastic to malignant human head and neck tissue. Furthermore, PKC expression correlates with poor prognosis in SCCHN. These results demonstrate that PKC regulates growth by stimulating DNA synthesis through cyclin E and E2F and identify PKC as a therapeutic target that is highly expressed in aggressive SCCHN. Keywords: time course; dose response
2009-03-22 | GSE10299 | GEO
Project description:mTORC1 is a conserved central controller of cell growth, which is commonly activated in hepatocellular carcinoma (HCC), driving liver tumorigenesis. In addition to its established cytoplasmic functions, mTORC1 is found in the nucleus where it regulates transcription by all three major RNA polymerases. However, precisely how mTORC1 controls gene expression remains poorly understood. Herein we show that mTORC1 interacts with the BAF SWI/SNF complex and regulates genome-wide chromatin remodeling through ARID1A. Mechanically, mTORC1 stimulates ubiquitination and proteasomal degradation of ARID1A protein through SCF ubiquitin ligase. mTORC1-ARID1A axis promotes chromatin remodeling and expression of YAP target genes, thereby enhancing oncogenic growth in vitro and in vivo. These findings reveal a novel nuclear mTORC1 function and the underlying mechanism that controls oncogenic chromatin remodeling to promote hepatocarcinogenesis.
2021-04-01 | GSE159163 | GEO
Project description:Ulp1 Regulates Cell Proliferation through INO1 in Pichia pastoris
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Project description:Protein arginine methylation is an important process, which regulates diverse cellular functions including cell proliferation, RNA stability, DNA repair and gene transcription. Based on literature search, protein arginine methyltransferase (PRMT) indeed plays important roles in colon cancer pathophysiology. The PRMT expression level is involved in colon cancer patient’s survival and has been suggested to be a prognostic marker in colon cancer patients. Recently, our group found a novel methylation on epidermal growth factor receptor (EGFR), which affected EGFR downstream signaling. investigators further observed the methylation event on EGFR not only regulated tumor growth in mouse xenograft model but also influenced cetuximab response in colon cancer cell lines. To further study the clinical correlation between EGFR methylation and cetuximab response, we propose to detect EGFR methylation level in paraffin embedded tissue samples from colorectal cancer patients with or without cetuximab treatment by IHC staining and analyze its correlation with cetuximab response. This study will provide an insight to the strategy of colorectal cancer therapy.
| 2157765 | ecrin-mdr-crc
Project description:Diverse cell types comprise animal tissues. However, the mechanisms controlling the number of each cell type within tissue compartments remain poorly understood. Here, we reported that different cell types utilize distinct strategies to control population numbers. Proliferation of fibroblasts, stromal cells important for tissue integrity, is limited by space availability. In contrast, proliferation of macrophages, innate immune cells involved in defense, repair, and homeostasis, is constrained by growth factor availability. Examination of density-dependent gene expression in fibroblasts revealed that Hippo and Tgf-b signaling are both regulated by cell density. We found YAP1, the transcriptional activator of the Hippo signaling pathway, directly regulate expression of Csf1, the lineage-specific growth factor for macrophages, through binding of YAP1 to a conserved enhancer of Csf1 that is specifically active in fibroblasts. Activation of YAP1 in fibroblasts elevates Csf1 expression, and is sufficient to increase the number of macrophages at steady state. Our data also suggest that expression programs in fibroblasts that change with density may result from sensing of mechanical pressure through actin-dependent mechanisms. Altogether, we demonstrate that two different modes of population control are connected and coordinated to regulate cell numbers of distinct cell types. Sensing of the tissue environment may serve as a general strategy to control tissue composition.
2022-07-21 | GSE184774 | GEO
Project description:Mitochondria are dynamic organelles that are important for cell growth and proliferation. Dysregulated mitochondrial dynamics are highly associated with the initiation and progression of various cancers, including ovarian cancer. However, the regulatory mechanism underlying mitochondrial dynamics is still not fully understood. Previously, our study showed that carnitine palmitoyltransferase 1A (CPT1A) is highly expressed in ovarian cancer cells and promotes the development of ovarian cancer. Here, we find that CPT1A regulates mitochondrial dynamics and promotes mitochondrial fission in ovarian cancer cells. Our study futher shows that CPT1A regulates mitochondrial fission and function through mitochondrial fission factor (MFF) to promote the growth and proliferation of ovarian cancer cells. Mechanistically, we show that CPT1A promotes succinylation of MFF at lysine 302 (K302), which protects against Parkin-mediated ubiquitin-proteasomal degradation of MFF. Finally, the study shows that MFF is highly expressed in ovarian cancer cells and that high MFF expression is associated with poor prognosis in patients with ovarian cancer. MFF inhibition significantly inhibits the progression of ovarian cancer in vivo. Overall, CPT1A regulates mitochondrial dynamics through MFF succinylation to promote the development of ovarian cancer. Moreover, our findings suggest that MFF is a potential therapeutic target for ovarian cancer.
2023-05-15 | PXD041990 | Pride
Project description:Tissue confinement regulates cell growth and size in epithelia
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