| First Author | Quinn HM | Year | 2021 |
| Journal | Cancer Res | Volume | 81 |
| Issue | 8 | Pages | 2116-2127 |
| PubMed ID | 33574090 | Mgi Jnum | J:305545 |
| Mgi Id | MGI:6706792 | Doi | 10.1158/0008-5472.CAN-20-2801 |
| Citation | Quinn HM, et al. (2021) YAP and beta-catenin cooperate to drive oncogenesis in basal breast cancer. Cancer Res |
| abstractText | Targeting cancer stem cells (CSC) can serve as an effective approach toward limiting resistance to therapies. While basal-like (triple-negative) breast cancers encompass cells with CSC features, rational therapies remain poorly established. We show here that the receptor tyrosine kinase Met promotes YAP activity in basal-like breast cancer and find enhanced YAP activity within the CSC population. Interfering with YAP activity delayed basal-like cancer formation, prevented luminal to basal trans-differentiation, and reduced CSC. YAP knockout mammary glands revealed a decrease in beta-catenin target genes, suggesting that YAP is required for nuclear beta-catenin activity. Mechanistically, nuclear YAP interacted with beta-catenin and TEAD4 at gene regulatory elements. Proteomic patient data revealed an upregulation of the YAP signature in basal-like breast cancers. Our findings demonstrate that in basal-like breast cancers, beta-catenin activity is dependent on YAP signalling and controls the CSC program. These findings suggest that targeting the YAP/TEAD4/beta-catenin complex offers a potential therapeutic strategy for eradicating CSCs in basal-like breast cancers. |
