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Common ELF1 deletion in prostate cancer bolsters oncogenic ETS function, inhibits senescence and promotes docetaxel resistance
- Source :
- Genes & Cancer
- Publication Year :
- 2018
- Publisher :
- Impact Journals, LLC, 2018.
-
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.
- Subjects :
- 0301 basic medicine
Senescence
chemotherapy resistance
Cancer Research
tumor suppressor
Biology
medicine.disease_cause
law.invention
03 medical and health sciences
Prostate cancer
0302 clinical medicine
law
Genetics
medicine
Gene
Transcription factor
Gene knockdown
ELF1
Cell migration
prostate cancer
medicine.disease
030104 developmental biology
030220 oncology & carcinogenesis
Cancer research
Suppressor
Carcinogenesis
Research Paper
ETS
Subjects
Details
- ISSN :
- 19476027
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Genes & Cancer
- Accession number :
- edsair.doi.dedup.....e0d5659b1cfd675427ce873a40240c7b