EGF Receptor Promotes Prostate Cancer Bone Metastasis by Downregulating miR-1 and Activating TWIST1.
Dysregulation of the EGFR signaling axis enhances bone metastases in many solid cancers. However, the relevant downstream effector signals in this axis are unclear. miR-1 was recently shown to function as a tumor suppressor in prostate cancer cells, where its expression correlated with reduced metastatic potential. In this study, we demonstrated a role for EGFR translocation in regulating transcription of miR-1-1, which directly targets expression of TWIST1. Consistent with these findings, we observed decreased miR-1 levels that correlated with enhanced expression of activated EGFR and TWIST1 in a cohort of human prostate cancer specimens and additional datasets. Our findings support a model in which nuclear EGFR acts as a transcriptional repressor to constrain the tumor-suppressive role of miR-1 and sustain oncogenic activation of TWIST1, thereby leading to accelerated bone metastasis.
Duke Scholars
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Related Subject Headings
- Xenograft Model Antitumor Assays
- Twist-Related Protein 1
- RNA Stability
- Prostatic Neoplasms
- Promoter Regions, Genetic
- Oncology & Carcinogenesis
- Nuclear Proteins
- MicroRNAs
- Mice, Nude
- Male
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Xenograft Model Antitumor Assays
- Twist-Related Protein 1
- RNA Stability
- Prostatic Neoplasms
- Promoter Regions, Genetic
- Oncology & Carcinogenesis
- Nuclear Proteins
- MicroRNAs
- Mice, Nude
- Male