EGF receptor promotes prostate cancer bone metastasis by downregulating miR-1 and activating TWIST1

Yung Sheng Chang, Wei Yu Chen, Juan Juan Yin, Heather Sheppard-Tillman, Jiaoti Huang, Yen Nien Liu

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59 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3077-3086
Number of pages10
JournalCancer Research
Volume75
Issue number15
DOIs
Publication statusPublished - Aug 1 2015

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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