A new research paper has been published in Volume 17. onco target March 17, 2026, entitled “CREB5 regulates a stem cell-like transcriptional program to promote tumor progression in prostate cancer.”
The study, led by corresponding authors Emmanuel S. Antonarakis and Justin Huang of the University of Minnesota Twin Cities School of Medicine and Masonic Cancer Center, examines how CREB5 shapes basal and stem cell-like transcriptional states in prostate cancer. The authors point out that approximately 30% to 40% of advanced prostate cancers harbor basal cell-like transcriptional programs and that stem cell-like tumors are a major mechanism of resistance to androgen receptor-targeted therapy.
Using transcriptome analysis of primary prostate cancer and castration-resistant prostate cancer cohorts (n = 493 and 208), the authors found that CREB5 expression was strongly correlated with basal-like gene signatures and stem cell-like transcriptional programs. CREB5 has also been shown to interact with AP-1 transcription factors and bind to regulatory elements of the AP-1 gene, suggesting a mechanistic role in promoting these aggressive tumor conditions. Functional experiments demonstrated that overexpression of CREB5 promoted colony formation and tumor growth, supporting the role of CREB5 in tumor progression.
”Taken together, this study shows that CREB5 promotes PC tumor progression through genes associated with SCL traits. ”
Mechanistically, this study shows that CREB5 regulates transcriptional programs associated with tumor progression and stem cell-like characteristics and is a central driver of the aggressive prostate cancer phenotype. This finding also suggests that CREB5 activity may already be present in primary tumors, potentially contributing to subsequent treatment resistance and disease progression.
The authors conclude that targeting the transcriptional program regulated by CREB5 may be a future strategy to address androgen receptor-independent prostate cancer. Further studies are needed to determine how disrupting CREB5 or its downstream pathways improves therapeutic response in advanced disease.
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Reference magazines:
Makovec, A. Others. (2026). CREB5 regulates stem cell-like transcriptional programs to promote tumor progression in prostate cancer. onco target. DOI: 10.18632/oncotarget.28826. https://www.oncotarget.com/article/28826/text/
