| First Author | Christin JR | Year | 2020 |
| Journal | Cell Rep | Volume | 31 |
| Issue | 10 | Pages | 107742 |
| PubMed ID | 32521267 | Mgi Jnum | J:306532 |
| Mgi Id | MGI:6715824 | Doi | 10.1016/j.celrep.2020.107742 |
| Citation | Christin JR, et al. (2020) Stem Cell Determinant SOX9 Promotes Lineage Plasticity and Progression in Basal-like Breast Cancer. Cell Rep 31(10):107742 |
| abstractText | Lineage plasticity is important for the development of basal-like breast cancer (BLBC), an aggressive cancer subtype. While BLBC is likely to originate from luminal progenitor cells, it acquires substantial basal cell features and contains a heterogenous collection of cells exhibiting basal, luminal, and hybrid phenotypes. Why luminal progenitors are prone to BLBC transformation and what drives luminal-to-basal reprogramming remain unclear. Here, we show that the transcription factor SOX9 acts as a determinant for estrogen-receptor-negative (ER(-)) luminal stem/progenitor cells (LSPCs). SOX9 controls LSPC activity in part by activating both canonical and non-canonical nuclear factor kappaB (NF-kappaB) signaling. Inactivation of TP53 and RB via expression of SV40 TAg in a BLBC mouse tumor model leads to upregulation of SOX9, which drives luminal-to-basal reprogramming in vivo. Furthermore, SOX9 deletion inhibits the progression of ductal carcinoma in situ (DCIS)-like lesions to invasive carcinoma. These data show that ER(-) LSPC determinant SOX9 acts as a lineage plasticity driver for BLBC progression. |
