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