Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

41 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Oncogene-like induction of cellular invasion from centrosome amplification

ABSTRACT: Centrosome amplification has long been recognized as a feature of human tumors, however its role in tumorigenesis remains unclear. Centrosome amplification is poorly tolerated by non-transformed cells, and, in the absence of selection, extra centrosomes are spontaneously lost. Thus, the high frequency of centrosome amplification, particularly in more aggressive tumors, raises the possibility that extra centrosomes could, in some contexts, confer advantageous characteristics that promote tumor progression. Using a three-dimensional model system and other approaches to culture human mammary epithelial cells, we find that centrosome amplification triggers cell invasion. This invasive behavior is similar to that induced by overexpression of the breast cancer oncogene ErbB2 and indeed enhances invasiveness triggered by ErbB2. We show that, through increased centrosomal microtubule nucleation, centrosome amplification increases Rac1 activity, which disrupts normal cell-cell adhesion and promotes invasion. These findings demonstrate that centrosome amplification, a structural alteration of the cytoskeleton, can promote features of malignant transformation. genome-wide human SNP 6.0 arrays from Affymetrix was used to determine the copy number changes of MCF10A cells with extra centrosomes or depleted of MCAK after grown 4 days in 3-D cultures

ORGANISM(S): Homo sapiens

SUBMITTER: Susana Godinho

PROVIDER: E-GEOD-55042 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Oncogene-like induction of cellular invasion from centrosome amplification

Project description:Centrosome amplification has long been recognized as a feature of human tumors, however its role in tumorigenesis remains unclear. Centrosome amplification is poorly tolerated by non-transformed cells, and, in the absence of selection, extra centrosomes are spontaneously lost. Thus, the high frequency of centrosome amplification, particularly in more aggressive tumors, raises the possibility that extra centrosomes could, in some contexts, confer advantageous characteristics that promote tumor progression. Using a three-dimensional model system and other approaches to culture human mammary epithelial cells, we find that centrosome amplification triggers cell invasion. This invasive behavior is similar to that induced by overexpression of the breast cancer oncogene ErbB2 and indeed enhances invasiveness triggered by ErbB2. We show that, through increased centrosomal microtubule nucleation, centrosome amplification increases Rac1 activity, which disrupts normal cell-cell adhesion and promotes invasion. These findings demonstrate that centrosome amplification, a structural alteration of the cytoskeleton, can promote features of malignant transformation.

2014-03-01 | GSE55042 | GEO

Gene expression comparison of MCF10A cells with and without extra centrosomes through overexpression of PLK4

Project description:The presence of extra centrosomes is a feature of human tumours. However, it is unclear what are the changes elicited by the presence of these abnormalities. To determine the changes in gene expression induced by centrosome amplification, human mammary epithelial cells, MCF10A, expressing a doxycycline inducible PLK4 cDNA were used. Centrosome amplification was induced for 48 hrs upon the addition of doxycyclin to the culture medium. RNA was purified from MCF10A cells without extra centrosomes (no dox) and with extra centrosomes (dox) and processed for microarray analysis.

2018-02-10 | E-MTAB-6415 | biostudies-arrayexpress

Centrosome amplification is sufficient to promote spontaneous tumorigenesis in mammals

Project description:Centrosome amplification is a common feature of human tumors, but whether this is a cause or a consequence of human cancer remains unclear. Here, we report the creation of a mouse model in which centrosome number can be persistently increased in the absence of additional genetic defects. We show that extra centrosomes increase tumor initiation in a mouse model of intestinal neoplasia. Most importantly, we demonstrate that supernumerary centrosomes are sufficient to drive development of spontaneous tumors in multiple tissues. Tumors with centrosome amplification exhibit frequent mitotic errors and possess complex karyotypes, recapitulating a common feature of human cancer. Together, our data support a direct causal relationship between centrosome amplification, genomic instability and tumor development. The sequences in this dataset result from random whole-genome DNA sequencing of spontaneous T- cell lymphomas, B-cell lymphomas, squamous cell carcinomas and one sarcoma from doxycycline-treated Plk4 mice.

2017-02-04 | E-MTAB-5043 | biostudies-arrayexpress

RNA-seq of cells with centrosome amplification

Project description:Centrosome amplification induces proliferation arrest and cell invasion. The fate of centrosome amplification cells are studied here.

2021-10-07 | E-MTAB-11126 | biostudies-arrayexpress

Gene expression in mitotic tissues of Drosophila larvae without centrosomes or too many centrosomes

2012-08-20 | GSE35240 | GEO

Gene expression in mitotic tissues of Drosophila larvae without centrosomes or too many centrosomes

Project description:Centrosome defects are a common feature of many cancers. Surprisingly, flies can proceed through the majority of development without centrosomes or with amplified centrosomes in most of their cells. It is unclear whether this is because centrosome defects do not cause many problems in Drosophila cells, or because they can adapt to cope with any problems that arise. Indeed, centrosome loss and centrosome amplification predispose fly brain cells to form tumours. Here we assess how centrosome loss or centrosome amplification perturbs cell physiology by profiling the global transcriptome of Drosophila larval brains and imaginal discs that either lack centrosomes or have too many centrosomes. Mitotic tissues (brains and imaginal discs) were dissected from 3rd instar Drosophila larvae of mutants lacking centrosomes (DSas-4 and DSas-6), a strain with too many centrosomes (SakOE) and two different wild type strains (w67 and OregonR). We extracted RNA from three biological replicates per strain and used it for hybridisation to Affymetrix Drosophila Genome 2.0 arrays. Per biological sample, material dissected from ten larvae was pooled. Gene expression of the mutant strains was compared to both wild type controls.

2012-08-20 | E-GEOD-35240 | biostudies-arrayexpress

Centrosome amplification triggers tumorigenesis in p53 deficient epidermis

Project description:While aneuploidy is found in more than 90% of solid tumors, it is unclear whether aneuploidy is the cause or the consequence of tumorigenesis. Different mouse models deficient in centrosomal or spindle checkpoint proteins that induce aneuploidy show either a promotion or a decrease in tumorigenesis depending on the tissues and the types of oncogenic stimuli. To investigate the effects of aneuploidy in skin development and tumorigenesis, we used Plk4 over-expression (Plk4OE) during epidermal development to assess centrosome amplification and aneuploidy. We found that PLK4OE in the developing epidermis induced centrosome amplification and multipolar divisions, consequently led to p53 stabilization and apoptosis of epidermal progenitors. This delayed epidermal stratification and induced lethal skin barrier defect in 50% of the mice. Plk4 transgene expression was shutdown postnatally in the surviving mice and PLK4OE mice never developed spontaneous skin tumors. Concomitant Plk4OE and P53 deletion (PLK4OE/p53cKO) rescued the defects in differentiation and stratification. Unexpectedly, p53 deletion did not rescue the apoptosis or eventual elimination of the cells overexpressing PLK4 and presenting multiple centrosomes. Remarkably, the short term presence of cells with supernumerary centrosomes postnatally was sufficient to generate aneuploidy and triggered spontaneous skin cancers with complete penetrance. These results reveal for the first time that aneuploidy induced by centrosome amplification, even if transient, can trigger tumorigenesis.

2015-10-27 | E-MTAB-3733 | biostudies-arrayexpress

Extra centrosomes induce PIDD1-mediated inflammation and Immunosurveillance

Project description:Unscheduled increases in cellular ploidy underlie defects in tissue function, premature aging, and malignancy. A concomitant event to polyploidization is the amplification of centrosomes, the main microtubule organization center in animal cells. Supernumerary centrosomes are frequent in tumors, correlating with higher aggressiveness and poor prognosis. However, extra centrosomes also exert an onco-protective effect by activating the p53 network and eliciting cell cycle arrest. Here, we report that extra centrosomes, arising during unscheduled polyploidization or aberrant centriole biogenesis, induce activation of NF-κB signaling and sterile inflammation. This signaling requires the NEMO-PIDDOsome, a multi-protein complex composed of PIDD1, RIPK1, and NEMO/IKKγ. Remarkably, the presence of supernumerary centrosomes suffices to induce a paracrine chemokine and cytokine profile, able to polarize macrophages into a pro-inflammatory phenotype. Furthermore, extra centrosomes, accumulating after cytokinesis failure, increase immunogenicity of cancer cells and render them more susceptible to NK-cell attack. Hence, extra centrosomes, the PIDDosome acts as a dual effector, able to engage not only the p53 network for cell cycle control but also NF-κB signaling to instruct innate immunity.

2023-08-21 | GSE235120 | GEO

Homo sapiens

Project description:Oncogene-like induction of cellular invasion from centrosome amplification

| PRJNA238351 | ENA

PCNA and JNK1-Stat3 pathways respectively promotes and inhibits centrosome amplification by targeting at the ROCK1/14-3-3σ complex

Project description:We have recently reported that type 2 diabetes promotes cell centrosome amplification via enhancing the expression, biding and centrosome translocation of ROCK1/14-3-3σ complex. In the present functional proteomic study, we further investigated the molecular pathways underlying the centrosome amplification using colon cancer HCT116 cells as experimental model. We found that treatment of cells with high glucose, insulin and palmitic acid triggered the centrosome amplification and increased the expressions of PCNA, NPM and 14-3-3σ. Individual knockdown of PCNA, NPM or 14-3-3σ inhibited the centrosome amplification. Knockdown of PCNA inhibited the treatment-increased expression of ROCK1, while knockdown of ROCK1 did not affect the PCNA expression. High glucose, insulin and palmitic acid also increased the expressions of JNK1 and Stat3, individual knockdown of which up-regulated the treatment-increased expression of 14-3-3σ and promoted the centrosome amplification. In contrast, over-expression of JNK1 inhibited the centrosome amplification. Knockdown of Stat3 enhanced the centrosome translocation of 14-3-3σ. Moreover, we showed that knockdown of JNK1 inhibited the treatment-increased expression of Stat3, but not the other way round. Knockdown of PCNA, JNK or Stat3 did not have an effect on NPM and vice versa. In conclusion, our results suggest that PCNA and JNK1-Stat3 pathways respectively promotes and feedback inhibits the centrosome amplification by targeting at the ROCK1/14-3-3σ complex, and NPM serves as an independent signal for the centrosome amplification.

2018-03-30 | PXD009370 | iProX

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data