The role of miR-203 and miR-34a in EGFR activation prostate cancer metastasis

Project: A - Government Institutiona - National Health Research Institutes

Project Details


Evidence suggests the acquisition of androgen-independence in prostate cancer may be due to upregulation of growth factor receptor signaling pathways, principally epidermal growth factor receptor (EGFR), making it an attractive target for therapeutic intervention. Although targeting membrane bound EGFR has shown some benefit, there is an emerging need to further explore targetable signaling components involved in the nuclear EGFR signaling network. Our proposed study shows the main function of nuclear EGFR appears to be an upstream factor for various oncogenic genes including TWIST1. Given the central role of EGFR in prostate bone metastasis, further characterizations of targets of EGFR-regulated genes are of interest. We hypothesized that the activation of EGFR pathway would induce TWIST1 activation and promote prostate bone metastasis. Our preliminary studies showed that activated-EGFR enhances prostate cancer progression and bone metastasis via down-regulation of a tumor suppressor, miR-1, and activation of TWIST1. To address the mechanism underlying the effects in tumor progression, we plan to demonstrate that miR-1 is directly and transcriptionally regulated by nuclear EGFR. Moreover, we will identify miR-1 targets in the 3′UTR of TWIST1 that can lead to TWIST1 down-regulation at both mRNA and protein levels. We will confirm our findings in patient tissue samples from low miR-1 prostate cancers by showing a positive correlation with enhanced TWIST1. Our studies will support a model that EGFR facilitates tumor malignancy through EGFR-dependent reduction of miR-1 to disrupt the inhibitory effects of miR-1-dependent post-transcriptional regulation of TWIST1 and enhance/or sustain TWIST1 activities.
Effective start/end date1/1/1512/31/15


  • prostate cancer
  • bone metastasis
  • signal transduction
  • drug resistance
  • transcription regulation
  • epigenetics
  • microRNA
  • microenvironment


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