| First Author | Al-Zahrani KN | Year | 2020 |
| Journal | Oncogene | Volume | 39 |
| Issue | 23 | Pages | 4592-4602 |
| PubMed ID | 32393835 | Mgi Jnum | J:290540 |
| Mgi Id | MGI:6441336 | Doi | 10.1038/s41388-020-1315-3 |
| Citation | Al-Zahrani KN, et al. (2020) Loss of the Ste20-like kinase induces a basal/stem-like phenotype in HER2-positive breast cancers. Oncogene 39(23):4592-4602 |
| abstractText | HER2 is overexpressed in 20-30% of all breast cancers and is associated with an invasive disease and poor clinical outcome. The Ste20-like kinase (SLK) is activated downstream of HER2/Neu and is required for efficient epithelial-to-mesenchymal transition, cell cycle progression, and migration in the mammary epithelium. Here we show that loss of SLK in a murine model of HER2/Neu-positive breast cancers significantly accelerates tumor onset and decreases overall survival. Transcriptional profiling of SLK knockout HER2/Neu-derived tumor cells revealed a strong induction in the triple-negative breast cancer marker, Sox10, accompanied by an increase in mammary stem/progenitor activity. Similarly, we demonstrate that SLK and Sox10 expression are inversely correlated in patient samples, with the loss of SLK and acquisition of Sox10 marking the triple-negative subtype. Furthermore, pharmacological inhibition of AKT reduces SLK-null tumor growth in vivo and is rescued by ectopic Sox10 expression, suggesting that Sox10 is a critical regulator of tumor growth downstream of SLK/AKT. These findings highlight a role for SLK in negatively regulating HER2-induced mammary tumorigenesis and provide mechanistic insight into the regulation of Sox10 expression in breast cancer. |
