PUBLICATION
Oxidative Stress in Cells with Extra Centrosomes Drives Non-Cell-Autonomous Invasion
- Authors
- Arnandis, T., Monteiro, P., Adams, S.D., Bridgeman, V.L., Rajeeve, V., Gadaleta, E., Marzec, J., Chelala, C., Malanchi, I., Cutillas, P.R., Godinho, S.A.
- ID
- ZDB-PUB-181127-24
- Date
- 2018
- Source
- Developmental Cell 47: 409-424.e9 (Journal)
- Registered Authors
- Keywords
- HER2, IL-8, ROS, cancer, centrosome amplification, invasion, paracrine signaling, secretion, senescence
- MeSH Terms
-
- Breast/metabolism
- Breast/pathology
- Cell Transformation, Neoplastic/pathology*
- Centrosome/metabolism
- Centrosome/pathology*
- Humans
- Mitosis/physiology*
- Neoplasms/pathology
- Oxidative Stress/physiology*
- Signal Transduction/physiology
- PubMed
- 30458137 Full text @ Dev. Cell
Citation
Arnandis, T., Monteiro, P., Adams, S.D., Bridgeman, V.L., Rajeeve, V., Gadaleta, E., Marzec, J., Chelala, C., Malanchi, I., Cutillas, P.R., Godinho, S.A. (2018) Oxidative Stress in Cells with Extra Centrosomes Drives Non-Cell-Autonomous Invasion. Developmental Cell. 47:409-424.e9.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping