“We determined that CREB5 is a key regulator of basal and SCL transcriptional programs and tumor-forming phenotypes in PC. ”
BUFFALO, NY – March 24, 2026 – A new research paper was published in Volume 17 of Oncotarget on March 17, 2026, titled “ CREB5 regulates stem cell-like transcriptional programs to enhance tumor progression in prostate cancer .”
Led by corresponding authors Emmanuel S. Antonarakis and Justin Hwang from the Department of Medicine and the Masonic Cancer Center at the University of Minnesota – Twin Cities, the study examines how CREB5 shapes basal-like and stem cell-like transcriptional states in prostate cancer. The authors note that about 30–40% of advanced prostate cancers harbor basal-like transcriptional programs, and that stem cell-like tumors are a major mechanism of resistance to androgen receptor-targeted therapies.
Using transcriptomic analyses of primary prostate cancer and castration-resistant prostate cancer cohorts (n = 493 and 208), the authors found that CREB5 expression strongly correlates with basal-like gene signatures and stem cell-like transcriptional programs. CREB5 was also shown to interact with AP-1 transcription factors and bind regulatory elements of AP-1 genes, suggesting a mechanistic role in promoting these aggressive tumor states. Functional experiments demonstrated that CREB5 overexpression enhances colony formation and tumor growth, supporting its role in tumor progression.
“ Taken together, this study indicates that CREB5 enhances PC tumor progression through genes that are associated with SCL traits.”
Mechanistically, the study shows that CREB5 regulates transcriptional programs linked to tumor progression and stem cell-like features, positioning it as a central driver of aggressive prostate cancer phenotypes. The findings also suggest that CREB5 activity may already be present in primary tumors, potentially contributing to later therapy resistance and disease progression.
The authors conclude that targeting CREB5-regulated transcriptional programs could represent a future strategy for addressing androgen receptor-independent prostate cancer. Further studies are needed to determine how disrupting CREB5 or its downstream pathways may improve therapeutic responses in advanced disease.
DOI: https://doi.org/10.18632/oncotarget.28826
Correspondence to: Emmanuel S. Antonarakis – anton401@umn.edu , and Justin Hwang – jhwang@umn.edu
Abstract video: https://www.youtube.com/watch?v=Zywrj5hV4ho
Keywords : cancer, prostate cancer, CREB5, basal-like, stem cell-like, AP-1 transcription factors
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CREB5 regulates stem cell-like transcriptional programs to enhance tumor progression in prostate cancer
17-Mar-2026
A.M. consults for EMRGNSE LLC. E.B. serves as a consultant for Astrin Biosciences, Tempus AI, and EMRGNSE LLC. H.E.B is a co-founder of EMRGNSE LLC. J.M.D. has no conflicts relevant to this work. However, he serves as Chief Scientific Officer of Astrin Biosciences. The interest related to J.M.D. has been reviewed and managed by the University of Minnesota in accordance with its Conflict-of-Interest policies. W.C.H is a consultant for Thermo Fischer, Solasta Ventures, KSQ Therapeutics, Frontier Medicines, Jubilant Therapeutics, Serinus Biosciences, Kestral Therapeutics, Weaver, Recursion Pharma, Crane Biotherapeutics, Function Oncology, and Perceptive. S.M.D. has served as a paid consultant/advisor to Janssen, Bristol Myers Squibb and Oncternal Therapeutics and as principal investigator on grants awarded to the University of Minnesota by Janssen and Pfizer/Astellas. E.S.A. reports grants and personal fees from Janssen, Sanofi, Bayer, Bristol Myers Squibb, Curium, MacroGenics, Merck, Pfizer, AstraZeneca, and Clovis; personal fees from Aadi Bioscience, Aikido Pharma, Astellas, Amgen, Blue Earth, Corcept Therapeutics, Exact Sciences, Hookipa Pharma, Invitae, Eli Lilly, Foundation Medicine, Menarini-Silicon Biosystems, Tango Therapeutics, Tempus, and Z-alpha; grants from Novartis, Celgene, and Orion; and has a patent for an AR-V7 biomarker technology that has been licensed to Qiagen. J.H. consults for Tempus AI and is a co-founder of EMRGNSE LLC.