Yen-Nien Liu
Taipei Medical University, Taiwan
Title: Loss of ETV6 expression results in aggressive prostate cancer progression: Modeling through prostate cancer cell lines
Biography
Biography: Yen-Nien Liu
Abstract
Loss of heterozygosity of ETV6, an ETS-family transcription factor in cancer suggests it acts as a tumor suppressor. However, its cellular functions and regulating signaling remain unclear. In this study, we demonstrate that ETV6 represses prostate cancer metastasis. We identified miR-96, a potential oncomiR, as a novel target of epidermal growth factor receptor (EGFR) signaling in prostate cancer cells. We further identified ETV6 as a downstream target of miR-96 and found that EGFR-mediated activation of miR-96 leads to decreased expression of ETV6. Activated-EGFR signaling mediated increases in miR-96 expression directly inhibited ETV6 expression. ETV6 knockdown promotes prostate cancer cells migration and invasion. Moreover, ectopic ETV6 expression was found associated with reduced metastasis of prostate cancer cells to both bone and brain and increased overall survival in a xenograft model. Importantly, we found EGFR serves as a transcriptioanl activator for miR-96 expression through nuclear EGFR binds to the primary miR-96 regulatory region. This mechanism is supported by results in clinical samples: Low ETV6 levels are correlated with high miR-96 and nuclear EGFR levels in tissue from prostate cancer patients. These studies suggest that prostatic metastasis involves EGFR-mediated miR-96 induction and ETV6 inactivation, resulting in metastatic phenotypes.