Centrosomal abnormalities, in particular centrosome amplification, are recurrent features of human tumors. Enforced centrosome amplification in vivo plays a role in tumor initiation and progression. However, centrosome amplification occurs only in a subset of cancer cells, and thus, partly due to this heterogeneity, the contribution of centrosome amplification to tumors is unknown. Here, we show that supernumerary centrosomes induce a paracrine-signaling axis via the secretion of proteins, including interleukin-8 (IL-8), which leads to non-cell-autonomous invasion in 3D mammary organoids and zebrafish models. This extra centrosomes-associated secretory phenotype (ECASP) promotes invasion of human mammary cells via HER2 signaling activation. Further, we demonstrate that centrosome amplification induces an early oxidative stress response via increased NOX-generated reactive oxygen species (ROS), which in turn mediates secretion of pro-invasive factors. The discovery that cells with extra centrosomes can manipulate the surrounding cells highlights unexpected and far-reaching consequences of these abnormalities in cancer.
Pubmed ID: 30458137 RIS Download
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View all literature mentionsInternational functional genomics data collection generated from microarray or next-generation sequencing (NGS) platforms. Repository of functional genomics data supporting publications. Provides genes expression data for reuse to the research community where they can be queried and downloaded. Integrated with the Gene Expression Atlas and the sequence databases at the European Bioinformatics Institute. Contains a subset of curated and re-annotated Archive data which can be queried for individual gene expression under different biological conditions across experiments. Data collected to MIAME and MINSEQE standards. Data are submitted by users or are imported directly from the NCBI Gene Expression Omnibus.
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View all literature mentionslaboratory mouse with name BALB/cAnNCrl from MGI.
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View all literature mentionsCell line BT-20 is a Cancer cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsCell line MCF-10A is a Spontaneously immortalized cell line with a species of origin Homo sapiens
View all literature mentionsThis polyclonal targets IgG (H+L)
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View all literature mentionsThis monoclonal targets Met
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View all literature mentionsThis polyclonal targets Erk1/2
View all literature mentionsThis monoclonal targets p44 / 42 MAP Kinase
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View all literature mentionsThis polyclonal targets CETN2
View all literature mentionsThis monoclonal targets α-Tubulin
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View all literature mentionsThis monoclonal targets Phospho-EGF Receptor (Tyr1068)
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View all literature mentionsThis monoclonal targets p21 Waf1/Cip1
View all literature mentionsThis monoclonal targets Actin, α-Smooth Muscle
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets IgG (H+L)
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