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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice

Published on: August 23, 2019

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Myeloid ERK5 deficiency suppresses tumor growth by blocking protumor macrophage polarization via STAT3 inhibition

Emanuele Giurisato1,2, Qiuping Xu2, Silvia Lonardi3

  • 1Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy; emanuele.giurisato@manchester.ac.uk cathy.tournier@manchester.ac.uk.

Proceedings of the National Academy of Sciences of the United States of America
|March 7, 2018
PubMed

Insights

Targeting extracellular-regulated protein kinase 5 (ERK5) reprograms tumor-associated macrophages (TAMs) to an antitumor state. Blocking ERK5 inhibits signal transducer and activator of transcription 3 (STAT3) signaling, halting cancer growth.

Area of Science:

  • Immunology
  • Cancer Biology
  • Molecular Signaling

Background:

  • Tumor-associated macrophages (TAMs) promote cancer progression, but effective targets to reduce their activity are limited.
  • The signaling pathways dictating protumor macrophage phenotypes are not well understood.
  • Macrophage-targeted therapies are a promising avenue in cancer immunotherapy.

Purpose of the Study:

  • To investigate the role of extracellular-regulated protein kinase 5 (ERK5) in determining macrophage polarity.
  • To explore ERK5 as a potential therapeutic target for reprogramming TAMs.

Main Methods:

  • Utilized myeloid ERK5-deficient mice to assess the impact on carcinoma graft growth.
  • Performed molecular analyses to investigate signaling pathways in ERK5-deficient TAMs.
  • Examined the effect of targeting ERK5 on macrophage transcriptional profiles.

Main Results:

  • Carcinoma graft growth was halted in myeloid ERK5-deficient mice.
  • Targeting ERK5 in macrophages induced a transcriptional shift towards proinflammatory mediators.
  • Activation of signal transducer and activator of transcription 3 (STAT3) via Tyr705 phosphorylation was impaired in ERK5-deleted TAMs.

Conclusions:

  • ERK5 plays a crucial role in regulating macrophage phenotype.
  • Blocking ERK5 can reprogram TAMs into an antitumor state.
  • Inhibition of ERK5-STAT3 signaling presents a potential cancer treatment strategy.
Keywords:
ERK5MAPKSTAT3macrophagestumors

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