CREB5 regulates stem cell-like transcriptional programs to enhance tumor progression in prostate cancer
Issued Date
2026-01-01
Resource Type
eISSN
19492553
Scopus ID
2-s2.0-105033774693
Journal Title
Oncotarget
Volume
17
Start Page
59
End Page
73
Rights Holder(s)
SCOPUS
Bibliographic Citation
Oncotarget Vol.17 (2026) , 59-73
Suggested Citation
Makovec A., Phoenix J.T., Bergom H.E., Boytim E., Gustafson A.P., Deacon A., Tape S., Ali A., Ludwig M., Pitzen S.P., Moline D., Richter C., Longie H., Su M.C., Jena S., Likasitwatanakul P., Drake J.M., Huang R.S., Hahn W.C., Rennhack J.P., Dehm S.M., Kregel S., Antonarakis E.S., Hwang J. CREB5 regulates stem cell-like transcriptional programs to enhance tumor progression in prostate cancer. Oncotarget Vol.17 (2026) , 59-73. 73. doi:10.18632/oncotarget.28826 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/115953
Title
CREB5 regulates stem cell-like transcriptional programs to enhance tumor progression in prostate cancer
Author's Affiliation
University of California, Los Angeles
University of Minnesota Twin Cities
University of Colorado Anschutz Medical Campus
Medical College of Wisconsin
Dana-Farber Cancer Institute
University of Kansas Medical Center
Loyola University Chicago
Broad Institute
Siriraj Hospital
Rush Medical College
Masonic Cancer Center
University of Minnesota Twin Cities
University of Colorado Anschutz Medical Campus
Medical College of Wisconsin
Dana-Farber Cancer Institute
University of Kansas Medical Center
Loyola University Chicago
Broad Institute
Siriraj Hospital
Rush Medical College
Masonic Cancer Center
Corresponding Author(s)
Other Contributor(s)
Abstract
Prostate gland cells can be transcriptionally and morphologically characterized as basal and luminal. About 30–40% of advanced prostate cancers (PC) harbor basal-like transcription programs. In castration-resistant PC (CRPC), studies indicate that basal and stem cell-like (SCL) tumors are major resistance mechanisms to androgen receptor (AR)-targeted therapies. SCL tumors have reduced AR activity and increased stem-cell activity that promotes tumor formation, which contributes to poor clinical outcomes. We determined that CREB5 is a key regulator of basal and SCL transcriptional programs and tumor-forming phenotypes in PC. Through in silico modeling of PC transcriptomes and several pre-defined PC signaling programs, CREB5 expression was best associated with basal-like gene signatures and SCL-associated genes in primary PC and CRPCs (n = 493 and 208). This included associations with FOSL1 and other AP-1 transcription factors. We further found that CREB5 interacted with AP-1 proteins and bound to the regulatory elements of AP-1 genes, suggesting a mechanistic role in regulating the activity of AP-1 genes. In AR-positive cells, CREB5 overexpression promoted cell colony growth with tumorigenic properties and increased tumor size in vivo. These findings implicate CREB5 as a driver of the transcriptional programs underlying AR-independent basal and SCL CRPC subtypes, and this activity is detectable in primary PC.