EGF Receptor Promotes Prostate Cancer Bone Metastasis by Downregulating miR-1 and Activating TWIST1.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Chang, Y-S; Chen, W-Y; Yin, JJ; Sheppard-Tillman, H; Huang, J; Liu, Y-N
Published Date
- August 1, 2015
Published In
Volume / Issue
- 75 / 15
Start / End Page
- 3077 - 3086
PubMed ID
- 26071255
Pubmed Central ID
- PMC4909124
Electronic International Standard Serial Number (EISSN)
- 1538-7445
Digital Object Identifier (DOI)
- 10.1158/0008-5472.CAN-14-3380
Language
- eng
Conference Location
- United States