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Induction and Analysis of Epithelial to Mesenchymal Transition
10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

36.5K

Interferon-induced IFIT5 promotes epithelial-to-mesenchymal transition leading to renal cancer invasion

U-Ging Lo1, Jiming Bao2, Junjie Cen3

  • 1Department of Urology, University of Texas Southwestern Medical Center Dallas, TX 75390, USA.

American Journal of Clinical and Experimental Urology
|March 26, 2019
PubMed

Insights

Interferon therapy may unexpectedly promote renal cell carcinoma (RCC) invasion by degrading tumor suppressor microRNAs, potentially hindering its clinical use. This study reveals a new pro-metastatic mechanism involving IFIT5 and epithelial-to-mesenchymal transition (EMT).

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Interferon (IFN) is a key factor in immunity and cancer therapy.
  • IFN therapy shows short-term response in renal cell carcinoma (RCC) but its adverse effects on RCC cells are unclear.

Purpose of the Study:

  • To investigate the potential adverse effects of IFNs on RCC cells.
  • To elucidate the mechanism by which IFNs might enhance RCC invasion.

Main Methods:

  • Investigated the role of IFIT5 in microRNA (miRNA) degradation.
  • Assessed the impact of IFN on Slug, ZEB1, and epithelial-to-mesenchymal transition (EMT) in RCC cells.
  • Analyzed IFNγ signaling pathway in metastatic RCC patient samples.

Main Results:

  • IFNs enhance RCC invasion through IFIT5-mediated degradation of tumor suppressor miRNAs.
  • This degradation leads to increased Slug and ZEB1 expression, promoting EMT.
  • Upregulation of IFNγ signaling pathway components (IFNGR1, IFNGR2, STAT1, STAT2) correlates with metastatic RCC.

Conclusions:

  • IFNs can promote RCC metastasis via a novel mechanism involving suppressor miRNA degradation.
  • This finding highlights a potential pro-metastatic effect of IFNs that may limit their use in RCC treatment.
Keywords:
Interferon (IFN)epithelial-to-mesenchymal transition (EMT)interferon-induced tetratricopeptide repeat 5 (IFIT5)

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