| Title | CREB5 Promotes Resistance to Androgen-Receptor Antagonists and Androgen Deprivation in Prostate Cancer. |
| Publication Type | Journal Article |
| Year of Publication | 2019 |
| Authors | Hwang JH, Seo J-H, Beshiri ML, Wankowicz S, Liu D, Cheung A, Li J, Qiu X, Hong AL, Botta G, Golumb L, Richter C, So J, Sandoval GJ, Giacomelli AO, Ly SHuong, Han C, Dai C, Pakula H, Sheahan A, Piccioni F, Gjoerup O, Loda M, Sowalsky AG, Ellis L, Long H, Root DE, Kelly K, Van Allen EM, Freedman ML, Choudhury AD, Hahn WC |
| Journal | Cell Rep |
| Volume | 29 |
| Issue | 8 |
| Pagination | 2355-2370.e6 |
| Date Published | 2019 11 19 |
| ISSN | 2211-1247 |
| Keywords | Androgen Receptor Antagonists, Antineoplastic Agents, Cyclic AMP Response Element-Binding Protein A, Drug Resistance, Neoplasm, Humans, Male, Open Reading Frames, Phenylthiohydantoin, Promoter Regions, Genetic, Prostatic Neoplasms, Castration-Resistant, Receptors, Androgen |
| Abstract | Androgen-receptor (AR) inhibitors, including enzalutamide, are used for treatment of all metastatic castration-resistant prostate cancers (mCRPCs). However, some patients develop resistance or never respond. We find that the transcription factor CREB5 confers enzalutamide resistance in an open reading frame (ORF) expression screen and in tumor xenografts. CREB5 overexpression is essential for an enzalutamide-resistant patient-derived organoid. In AR-expressing prostate cancer cells, CREB5 interactions enhance AR activity at a subset of promoters and enhancers upon enzalutamide treatment, including MYC and genes involved in the cell cycle. In mCRPC, we found recurrent amplification and overexpression of CREB5. Our observations identify CREB5 as one mechanism that drives resistance to AR antagonists in prostate cancers. |
| DOI | 10.1016/j.celrep.2019.10.068 |
| Alternate Journal | Cell Rep |
| PubMed ID | 31747605 |
| PubMed Central ID | PMC6886683 |
| Grant List | U01 CA176058 / CA / NCI NIH HHS / United States K08 CA188615 / CA / NCI NIH HHS / United States |
Related Faculty:
Massimo Loda, M.D.