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RIG-like Helicase Regulation of Chitinase 3-like 1 Axis and Pulmonary Metastasis

Bing Ma1, Erica L Herzog2, Meagan Moore2

  • 1Department of Molecular Microbiology and Immunology, Brown University, Providence, R.I. 02912, USA.

Scientific Reports
|May 21, 2016
PubMed

Insights

The RIG-like helicase (RLH) innate immune response inhibits cancer-promoting Chi3l1 and metastasis. RLH activation abrogates Chi3l1

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Chitinase 3-like 1 (Chi3l1) is linked to poor cancer prognosis and metastasis.
  • Mechanisms of Chi3l1 in tumor progression and its regulatory pathways are not fully understood.

Purpose of the Study:

  • To investigate how Chi3l1 promotes tumor progression and metastasis.
  • To determine if the RIG-like helicase (RLH) innate immune response can control Chi3l1 and metastasis.

Main Methods:

  • Characterization of Chi3l1-mediated tumor progression mechanisms.
  • Assessment of RLH activation's effect on Chi3l1, metastasis, and immune responses.
  • MAVS-dependent pathway analysis.

Main Results:

  • RLH activation suppressed tumor-induced Chi3l1 and IL-13Rα2 expression, inhibiting pulmonary metastasis.
  • RLH restored NK cell activity, increased IFN-α/β, chemerin/ChemR23, p-cofilin, LIMK2, and PTEN.
  • RLH inhibited BRAF and NLRX1 expression in a MAVS-dependent manner.

Conclusions:

  • Chi3l1 acts as a multifaceted immune stimulator promoting tumor progression and metastasis.
  • RLH innate immune responses effectively abrogate Chi3l1's tumor-promoting effects and metastasis.

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