Epidermal growth factor receptor signaling promotes metastatic prostate cancer through microRNA-96-mediated downregulation of the tumor suppressor ETV6

Yuan Chin Tsai, Wei Yu Chen, Man Kit Siu, Hong Yuan Tsai, Juan Juan Yin, Jiaoti Huang, Yen Nien Liu

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

It has been suggested that ETV6 serves as a tumor suppressor; however, its molecular regulation and cellular functions remain unclear. We used prostate cancer as a model system and demonstrated a molecular mechanism in which ETV6 can be regulated by epidermal growth factor receptor (EGFR) signaling through microRNA-96 (miR-96)-mediated downregulation. In addition, EGFR acts as a transcriptional coactivator that binds to the promoter of primary miR-96 and transcriptionally regulates miR-96 levels. We analyzed two sets of clinical prostate cancer samples, confirmed association patterns that were consistent with the EGFR-miR-96-ETV6 signaling model and demonstrated that the reduced ETV6 levels were associated with malignant prostate cancer. Based on results derived from multiple approaches, we identified the biological functions of ETV6 as a tumor suppressor that inhibits proliferation and metastasis in prostate cancer. We present a molecular mechanism in which EGFR activation leads to the induction of miR-96 expression and suppression of ETV6, which contributes to prostate cancer progression.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalCancer Letters
Volume384
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

MicroRNAs
Epidermal Growth Factor Receptor
Prostatic Neoplasms
Down-Regulation
Neoplasms
Neoplasm Metastasis

Keywords

  • Bone metastasis
  • Epidermal growth factor receptor (EGFR)
  • ETV6
  • microRNA (miR)-96
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Epidermal growth factor receptor signaling promotes metastatic prostate cancer through microRNA-96-mediated downregulation of the tumor suppressor ETV6. / Tsai, Yuan Chin; Chen, Wei Yu; Siu, Man Kit; Tsai, Hong Yuan; Yin, Juan Juan; Huang, Jiaoti; Liu, Yen Nien.

In: Cancer Letters, Vol. 384, 01.01.2017, p. 1-8.

Research output: Contribution to journalArticle

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AU - Siu, Man Kit

AU - Tsai, Hong Yuan

AU - Yin, Juan Juan

AU - Huang, Jiaoti

AU - Liu, Yen Nien

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AB - It has been suggested that ETV6 serves as a tumor suppressor; however, its molecular regulation and cellular functions remain unclear. We used prostate cancer as a model system and demonstrated a molecular mechanism in which ETV6 can be regulated by epidermal growth factor receptor (EGFR) signaling through microRNA-96 (miR-96)-mediated downregulation. In addition, EGFR acts as a transcriptional coactivator that binds to the promoter of primary miR-96 and transcriptionally regulates miR-96 levels. We analyzed two sets of clinical prostate cancer samples, confirmed association patterns that were consistent with the EGFR-miR-96-ETV6 signaling model and demonstrated that the reduced ETV6 levels were associated with malignant prostate cancer. Based on results derived from multiple approaches, we identified the biological functions of ETV6 as a tumor suppressor that inhibits proliferation and metastasis in prostate cancer. We present a molecular mechanism in which EGFR activation leads to the induction of miR-96 expression and suppression of ETV6, which contributes to prostate cancer progression.

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