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Updated: Jan 31, 2026
Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
Common ELF1 deletion in prostate cancer bolsters oncogenic ETS function, inhibits senescence and promotes docetaxel
Justin A Budka1, Mary W Ferris1, Matthew J Capone1
1Medical Sciences, Indiana University School of Medicine, Bloomington, Indiana, USA.
Abstract:
ETS family transcription factors play major roles in prostate tumorigenesis with some acting as oncogenes and others as tumor suppressors. ETS factors can compete for binding at some cis-regulatory sequences, but display specific binding at others. Therefore, changes in expression of ETS family members during tumorigenesis can have complex, multimodal effects. Here we show that ELF1 was the most commonly down-regulated ETS factor in primary prostate tumors, and expression decreased further in metastatic disease. Genome-wide mapping in cell lines indicated that ELF1 has two distinct tumor suppressive roles mediated by distinct cis-regulatory sequences. First, ELF1 inhibited cell migration and epithelial-mesenchymal transition by interfering with oncogenic ETS functions at ETS/AP-1 cis-regulatory motifs. Second, ELF1 uniquely targeted and activated genes that promote senescence. Furthermore, knockdown of ELF1 increased docetaxel resistance, indicating that the genomic deletions found in metastatic prostate tumors may promote therapeutic resistance through loss of both RB1 and ELF1.
Insights
ELF1, a key transcription factor, is frequently downregulated in prostate cancer, hindering tumor suppression and promoting metastasis. Loss of ELF1 also increases resistance to docetaxel therapy, suggesting a role in treatment failure.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- ETS transcription factors are critical in prostate cancer, acting as oncogenes or tumor suppressors.
- Altered ETS factor expression significantly impacts prostate tumorigenesis due to complex binding dynamics.
- ELF1 is identified as a commonly downregulated ETS factor in primary and metastatic prostate tumors.
Purpose of the Study:
- To elucidate the tumor-suppressive roles of ELF1 in prostate cancer.
- To investigate the mechanisms by which ELF1 loss contributes to prostate tumorigenesis and therapeutic resistance.
Main Methods:
- Genome-wide mapping of ELF1 binding sites in prostate cancer cell lines.
- Analysis of ELF1's effects on cell migration, epithelial-mesenchymal transition, and senescence.
- Assessment of ELF1 knockdown effects on docetaxel resistance.
Main Results:
- ELF1 exhibits two distinct tumor-suppressive functions mediated by specific cis-regulatory elements.
- ELF1 inhibits cell migration and epithelial-mesenchymal transition by opposing oncogenic ETS factors at ETS/AP-1 motifs.
- ELF1 uniquely targets and activates senescence-promoting genes, and its loss confers docetaxel resistance.
Conclusions:
- Downregulation of ELF1 contributes to prostate cancer progression and metastasis.
- ELF1 loss promotes therapeutic resistance, potentially through combined loss with RB1 in metastatic disease.
- ELF1 represents a potential therapeutic target for overcoming treatment resistance in prostate cancer.
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