Cargando…
CREB5 Promotes Resistance to Androgen-Receptor Antagonists and Androgen Deprivation in Prostate Cancer
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 readi...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2019
|
| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886683/ https://www.ncbi.nlm.nih.gov/pubmed/31747605 http://dx.doi.org/10.1016/j.celrep.2019.10.068 |
| _version_ | 1783474910204526592 |
|---|---|
| author | Hwang, Justin H. Seo, Ji-Heui Beshiri, Michael L. Wankowicz, Stephanie Liu, David Cheung, Alexander Li, Ji Qiu, Xintao Hong, Andrew L. Botta, Ginevra Golumb, Lior Richter, Camden So, Jonathan Sandoval, Gabriel J. Giacomelli, Andrew O. Ly, Seav Huong Han, Celine Dai, Chao Pakula, Hubert Sheahan, Anjali Piccioni, Federica Gjoerup, Ole Loda, Massimo Sowalsky, Adam G. Ellis, Leigh Long, Henry Root, David E. Kelly, Kathleen Van Allen, Eliezer M. Freedman, Matthew L. Choudhury, Atish D. Hahn, William C. |
| author_facet | Hwang, Justin H. Seo, Ji-Heui Beshiri, Michael L. Wankowicz, Stephanie Liu, David Cheung, Alexander Li, Ji Qiu, Xintao Hong, Andrew L. Botta, Ginevra Golumb, Lior Richter, Camden So, Jonathan Sandoval, Gabriel J. Giacomelli, Andrew O. Ly, Seav Huong Han, Celine Dai, Chao Pakula, Hubert Sheahan, Anjali Piccioni, Federica Gjoerup, Ole Loda, Massimo Sowalsky, Adam G. Ellis, Leigh Long, Henry Root, David E. Kelly, Kathleen Van Allen, Eliezer M. Freedman, Matthew L. Choudhury, Atish D. Hahn, William C. |
| author_sort | Hwang, Justin H. |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-6886683 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2019 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-68866832019-12-03 CREB5 Promotes Resistance to Androgen-Receptor Antagonists and Androgen Deprivation in Prostate Cancer Hwang, Justin H. Seo, Ji-Heui Beshiri, Michael L. Wankowicz, Stephanie Liu, David Cheung, Alexander Li, Ji Qiu, Xintao Hong, Andrew L. Botta, Ginevra Golumb, Lior Richter, Camden So, Jonathan Sandoval, Gabriel J. Giacomelli, Andrew O. Ly, Seav Huong Han, Celine Dai, Chao Pakula, Hubert Sheahan, Anjali Piccioni, Federica Gjoerup, Ole Loda, Massimo Sowalsky, Adam G. Ellis, Leigh Long, Henry Root, David E. Kelly, Kathleen Van Allen, Eliezer M. Freedman, Matthew L. Choudhury, Atish D. Hahn, William C. Cell Rep Article 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. 2019-11-19 /pmc/articles/PMC6886683/ /pubmed/31747605 http://dx.doi.org/10.1016/j.celrep.2019.10.068 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| spellingShingle | Article Hwang, Justin H. Seo, Ji-Heui Beshiri, Michael L. Wankowicz, Stephanie Liu, David Cheung, Alexander Li, Ji Qiu, Xintao Hong, Andrew L. Botta, Ginevra Golumb, Lior Richter, Camden So, Jonathan Sandoval, Gabriel J. Giacomelli, Andrew O. Ly, Seav Huong Han, Celine Dai, Chao Pakula, Hubert Sheahan, Anjali Piccioni, Federica Gjoerup, Ole Loda, Massimo Sowalsky, Adam G. Ellis, Leigh Long, Henry Root, David E. Kelly, Kathleen Van Allen, Eliezer M. Freedman, Matthew L. Choudhury, Atish D. Hahn, William C. CREB5 Promotes Resistance to Androgen-Receptor Antagonists and Androgen Deprivation in Prostate Cancer |
| title | CREB5 Promotes Resistance to Androgen-Receptor Antagonists and Androgen Deprivation in Prostate Cancer |
| title_full | CREB5 Promotes Resistance to Androgen-Receptor Antagonists and Androgen Deprivation in Prostate Cancer |
| title_fullStr | CREB5 Promotes Resistance to Androgen-Receptor Antagonists and Androgen Deprivation in Prostate Cancer |
| title_full_unstemmed | CREB5 Promotes Resistance to Androgen-Receptor Antagonists and Androgen Deprivation in Prostate Cancer |
| title_short | CREB5 Promotes Resistance to Androgen-Receptor Antagonists and Androgen Deprivation in Prostate Cancer |
| title_sort | creb5 promotes resistance to androgen-receptor antagonists and androgen deprivation in prostate cancer |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886683/ https://www.ncbi.nlm.nih.gov/pubmed/31747605 http://dx.doi.org/10.1016/j.celrep.2019.10.068 |
| work_keys_str_mv | AT hwangjustinh creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT seojiheui creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT beshirimichaell creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT wankowiczstephanie creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT liudavid creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT cheungalexander creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT liji creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT qiuxintao creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT hongandrewl creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT bottaginevra creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT golumblior creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT richtercamden creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT sojonathan creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT sandovalgabrielj creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT giacomelliandrewo creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT lyseavhuong creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT hanceline creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT daichao creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT pakulahubert creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT sheahananjali creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT piccionifederica creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT gjoerupole creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT lodamassimo creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT sowalskyadamg creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT ellisleigh creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT longhenry creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT rootdavide creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT kellykathleen creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT vanalleneliezerm creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT freedmanmatthewl creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT choudhuryatishd creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer AT hahnwilliamc creb5promotesresistancetoandrogenreceptorantagonistsandandrogendeprivationinprostatecancer |