Aurora A (serine/threonine kinase 6) is overexpressed in many pre-invasive and invasive breast carcinomas. High expression of Aurora A is strongly associated with decreased survival in patients with breast cancer, but the molecular mechanisms that underlie Aurora-A-associated malignancy are poorly understood. Here, Kavita Shah and co-workers (p. 2711) use a new chemical genetic approach to identify the pleckstrin-homology-like domain protein PHLDA1 as a putative Aurora A target. The authors confirm previous reports that PHLDA1 is frequently downregulated in primary breast cancers and, in addition, show that PHLDA1 downregulation is associated with oestrogen receptor expression in breast carcinoma. Aurora A directly phosphorylates PHLDA1, which leads to its degradation, but PHLDA1 also negatively regulates Aurora A, thereby setting up a feedback loop. Finally, they show that PHLDA1 upregulation and Aurora A inhibition act synergistically to promote cell death, and that PHLDA1 strongly inhibits the motility, proliferation and transformation of breast cancer cells. Thus, the authors suggest, PHLDA1 phosphorylation is one of the key ways in which Aurora A promotes breast malignancy. PHLDA1 overexpression could, therefore, provide a new way to modulate Aurora A deregulation in breast cancer.

• © 2011.