| First Author | Kim WK | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 4364 |
| PubMed ID | 35902588 | Mgi Jnum | J:327072 |
| Mgi Id | MGI:7328085 | Doi | 10.1038/s41467-022-32119-0 |
| Citation | Kim WK, et al. (2022) Aberrant androgen action in prostatic progenitor cells induces oncogenesis and tumor development through IGF1 and Wnt axes. Nat Commun 13(1):4364 |
| abstractText | Androgen/androgen receptor (AR) signaling pathways are essential for prostate tumorigenesis. However, the fundamental mechanisms underlying the AR functioning as a tumor promoter in inducing prostatic oncogenesis still remain elusive. Here, we demonstrate that a subpopulation of prostatic Osr1 (odd skipped-related 1)-lineage cells functions as tumor progenitors in prostate tumorigenesis. Single cell transcriptomic analyses reveal that aberrant AR activation in these cells elevates insulin-like growth factor 1 (IGF1) signaling pathways and initiates oncogenic transformation. Elevating IGF1 signaling further cumulates Wnt/beta-catenin pathways in transformed cells to promote prostate tumor development. Correlations between altered androgen, IGF1, and Wnt/beta-catenin signaling are also identified in human prostate cancer samples, uncovering a dynamic regulatory loop initiated by the AR through prostate cancer development. Co-inhibition of androgen and Wnt-signaling pathways significantly represses the growth of AR-positive tumor cells in both ex-vivo and in-vivo, implicating co-targeting therapeutic strategies for these pathways to treat advanced prostate cancer. |
