| First Author | Mohamed GA | Year | 2023 |
| Journal | Breast Cancer Res | Volume | 25 |
| Issue | 1 | Pages | 23 |
| PubMed ID | 36859337 | Mgi Jnum | J:376172 |
| Mgi Id | MGI:8269086 | Doi | 10.1186/s13058-023-01621-8 |
| Citation | Mohamed GA, et al. (2023) Lineage plasticity enables low-ER luminal tumors to evolve and gain basal-like traits. Breast Cancer Res 25(1):23 |
| abstractText | Stratifying breast cancer into specific molecular or histologic subtypes aids in therapeutic decision-making and predicting outcomes; however, these subtypes may not be as distinct as previously thought. Patients with luminal-like, estrogen receptor (ER)-expressing tumors have better prognosis than patients with more aggressive, triple-negative or basal-like tumors. There is, however, a subset of luminal-like tumors that express lower levels of ER, which exhibit more basal-like features. We have found that breast tumors expressing lower levels of ER, traditionally considered to be luminal-like, represent a distinct subset of breast cancer characterized by the emergence of basal-like features. Lineage tracing of low-ER tumors in the MMTV-PyMT mouse mammary tumor model revealed that basal marker-expressing cells arose from normal luminal epithelial cells, suggesting that luminal-to-basal plasticity is responsible for the evolution and emergence of basal-like characteristics. This plasticity allows tumor cells to gain a new lumino-basal phenotype, thus leading to intratumoral lumino-basal heterogeneity. Single-cell RNA sequencing revealed SOX10 as a potential driver for this plasticity, which is known among breast tumors to be almost exclusively expressed in triple-negative breast cancer (TNBC) and was also found to be highly expressed in low-ER tumors. These findings suggest that basal-like tumors may result from the evolutionary progression of luminal tumors with low ER expression. |
