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

Publication ,  Journal Article
Tsai, Y-C; Chen, W-Y; Siu, MK; Tsai, H-Y; Yin, JJ; Huang, J; Liu, Y-N
Published in: Cancer Lett
January 1, 2017

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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Published In

Cancer Lett

DOI

EISSN

1872-7980

Publication Date

January 1, 2017

Volume

384

Start / End Page

1 / 8

Location

Ireland

Related Subject Headings

  • Transfection
  • Transcription, Genetic
  • Time Factors
  • Signal Transduction
  • Repressor Proteins
  • RNA, Messenger
  • RNA Stability
  • RNA Interference
  • Proto-Oncogene Proteins c-ets
  • Prostatic Neoplasms
 

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Tsai, Y.-C., Chen, W.-Y., Siu, M. K., Tsai, H.-Y., Yin, J. J., Huang, J., & Liu, Y.-N. (2017). Epidermal growth factor receptor signaling promotes metastatic prostate cancer through microRNA-96-mediated downregulation of the tumor suppressor ETV6. Cancer Lett, 384, 1–8. https://doi.org/10.1016/j.canlet.2016.10.014
Tsai, Yuan-Chin, Wei-Yu Chen, Man Kit Siu, Hong-Yuan Tsai, Juan Juan Yin, Jiaoti Huang, and Yen-Nien Liu. “Epidermal growth factor receptor signaling promotes metastatic prostate cancer through microRNA-96-mediated downregulation of the tumor suppressor ETV6.Cancer Lett 384 (January 1, 2017): 1–8. https://doi.org/10.1016/j.canlet.2016.10.014.
Tsai, Yuan-Chin, et al. “Epidermal growth factor receptor signaling promotes metastatic prostate cancer through microRNA-96-mediated downregulation of the tumor suppressor ETV6.Cancer Lett, vol. 384, Jan. 2017, pp. 1–8. Pubmed, doi:10.1016/j.canlet.2016.10.014.
Journal cover image

Published In

Cancer Lett

DOI

EISSN

1872-7980

Publication Date

January 1, 2017

Volume

384

Start / End Page

1 / 8

Location

Ireland

Related Subject Headings

  • Transfection
  • Transcription, Genetic
  • Time Factors
  • Signal Transduction
  • Repressor Proteins
  • RNA, Messenger
  • RNA Stability
  • RNA Interference
  • Proto-Oncogene Proteins c-ets
  • Prostatic Neoplasms