| First Author | Arnandis T | Year | 2018 |
| Journal | Dev Cell | Volume | 47 |
| Issue | 4 | Pages | 409-424.e9 |
| PubMed ID | 30458137 | Mgi Jnum | J:272537 |
| Mgi Id | MGI:6284986 | Doi | 10.1016/j.devcel.2018.10.026 |
| Citation | Arnandis T, et al. (2018) Oxidative Stress in Cells with Extra Centrosomes Drives Non-Cell-Autonomous Invasion. Dev Cell 47(4):409-424.e9 |
| abstractText | 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. |
