| First Author | Tabrizian N | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 8 | Pages | 112937 |
| PubMed ID | 37552603 | Mgi Jnum | J:353761 |
| Mgi Id | MGI:7525082 | Doi | 10.1016/j.celrep.2023.112937 |
| Citation | Tabrizian N, et al. (2023) ASCL1 is activated downstream of the ROR2/CREB signaling pathway to support lineage plasticity in prostate cancer. Cell Rep 42(8):112937 |
| abstractText | Lineage plasticity is a form of therapy-induced drug resistance. In prostate cancer, androgen receptor (AR) pathway inhibitors potentially lead to the accretion of tumor relapse with loss of AR signaling and a shift from a luminal state to an alternate program. However, the molecular and signaling mechanisms orchestrating the development of lineage plasticity under the pressure of AR-targeted therapies are not fully understood. Here, a survey of receptor tyrosine kinases (RTKs) identifies ROR2 as the top upregulated RTK following AR pathway inhibition, which feeds into lineage plasticity by promoting stem-cell-like and neuronal networks. Mechanistically, ROR2 activates the ERK/CREB signaling pathway to modulate the expression of the lineage commitment transcription factor ASCL1. Collectively, our findings nominate ROR2 as a potential therapeutic target to reverse the ENZ-induced plastic phenotype and potentially re-sensitize tumors to AR pathway inhibitors. |
