10779/crick.12498035.v1
Teresa Arnandis
Teresa
Arnandis
Pedro Monteiro
Pedro
Monteiro
Sophie D Adams
Sophie D
Adams
Victoria Louise Bridgeman
Victoria Louise
Bridgeman
Vinothini Rajeeve
Vinothini
Rajeeve
Emanuela Gadaleta
Emanuela
Gadaleta
Jacek Marzec
Jacek
Marzec
Claude Chelala
Claude
Chelala
Ilaria Malanchi
Ilaria
Malanchi
Pedro R Cutillas
Pedro R
Cutillas
Susana A Godinho
Susana A
Godinho
Oxidative stress in cells with extra centrosomes drives non-cell-autonomous invasion
The Francis Crick Institute
2020
HER2
IL-8
ROS
cancer
centrosome amplification
invasion
paracrine signaling
secretion
senescence
Breast
Cell Transformation, Neoplastic
Centrosome
Humans
Mitosis
Neoplasms
Oxidative Stress
Signal Transduction
Malanchi FC001112
06 Biological Sciences
11 Medical and Health Sciences
Developmental Biology
2020-06-25 15:18:08
Journal contribution
https://crick.figshare.com/articles/journal_contribution/Oxidative_stress_in_cells_with_extra_centrosomes_drives_non-cell-autonomous_invasion/12498035
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.