| First Author | Johnson EO | Year | 2012 |
| Journal | J Cell Sci | Volume | 125 |
| Issue | Pt 5 | Pages | 1204-16 |
| PubMed ID | 22492986 | Mgi Jnum | J:197790 |
| Mgi Id | MGI:5494536 | Doi | 10.1242/jcs.092304 |
| Citation | Johnson EO, et al. (2012) LIMK2 is a crucial regulator and effector of Aurora-A-kinase-mediated malignancy. J Cell Sci 125(Pt 5):1204-16 |
| abstractText | Aurora A is overexpressed in majority of breast carcinomas. With the exception of BRCA1 and PHLDA1, no oncogenic Aurora A substrates are known in breast cancer. In this study, a chemical genetic approach was used to identify malignant targets of Aurora A, which revealed LIMK2 as a novel Aurora A substrate. Aurora A regulates LIMK2 kinase activity, subcellular localization and protein levels by direct phosphorylation at S283, T494 and T505. In response, LIMK2 also positively regulates the level of Aurora A, thereby engaging in a positive-feedback loop, promoting Aurora-A-mediated oncogenic pathways. Most importantly, LIMK2 ablation fully abrogates Aurora-A-mediated tumorigenesis in nude mice, suggesting that LIMK2 is a key oncogenic effector of Aurora A. Furthermore, LIMK2 ablation acts synergistically with inhibition of Aurora A in promoting cell death. Finally, Aurora-A-mediated upregulation of LIMK2 appears to be a common mechanism in many cancers. LIMK2 inhibition or ablation is therefore an alternative approach for modulating Aurora A deregulation in cancer. |
