| First Author | Gulluni F | Year | 2017 |
| Journal | Cancer Cell | Volume | 32 |
| Issue | 4 | Pages | 444-459.e7 |
| PubMed ID | 29017056 | Mgi Jnum | J:245586 |
| Mgi Id | MGI:5917906 | Doi | 10.1016/j.ccell.2017.09.002 |
| Citation | Gulluni F, et al. (2017) Mitotic Spindle Assembly and Genomic Stability in Breast Cancer Require PI3K-C2alpha Scaffolding Function. Cancer Cell 32(4):444-459.e7 |
| abstractText | Proper organization of the mitotic spindle is key to genetic stability, but molecular components of inter-microtubule bridges that crosslink kinetochore fibers (K-fibers) are still largely unknown. Here we identify a kinase-independent function of class II phosphoinositide 3-OH kinase alpha (PI3K-C2alpha) acting as limiting scaffold protein organizing clathrin and TACC3 complex crosslinking K-fibers. Downregulation of PI3K-C2alpha causes spindle alterations, delayed anaphase onset, and aneuploidy, indicating that PI3K-C2alpha expression is required for genomic stability. Reduced abundance of PI3K-C2alpha in breast cancer models initially impairs tumor growth but later leads to the convergent evolution of fast-growing clones with mitotic checkpoint defects. As a consequence of altered spindle, loss of PI3K-C2alpha increases sensitivity to taxane-based therapy in pre-clinical models and in neoadjuvant settings. |
