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Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma
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ADAM17 Activity and IL-6 Trans-Signaling in Inflammation and Cancer

Neele Schumacher1, Stefan Rose-John1

  • 1Biochemical Institute, University of Kiel, 24118 Kiel, Germany.

Cancers
|November 8, 2019
PubMed

Insights

Blocking IL-6 trans-signaling effectively inhibits colon cancer by targeting epidermal growth factor receptor (EGF-R) activity on myeloid cells. This approach offers a new therapeutic strategy for EGF-R-related cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Epidermal growth factor receptor (EGF-R) ligands are transmembrane proteins requiring proteolytic cleavage for systemic activity.
  • ADAM17 is a key metalloprotease involved in cleaving EGF-R ligands, TNFα, and IL-6 receptor.
  • EGF-R activity on myeloid cells, not epithelial cells, drives colon cancer formation.

Purpose of the Study:

  • To investigate the role of ADAM17 and IL-6 trans-signaling in EGF-R-mediated colon cancer.
  • To explore therapeutic strategies targeting downstream pathways of EGF-R in colon cancer.

Main Methods:

  • Analysis of colon cancer formation in the absence of ADAM17.
  • Investigating the role of IL-6 synthesis and IL-6 trans-signaling.
  • Evaluating the efficacy of sgp130Fc, an IL-6 trans-signaling inhibitor.

Main Results:

  • Colon cancer formation is significantly reduced in the absence of ADAM17.
  • EGF-R signaling on myeloid cells stimulates IL-6 synthesis.
  • IL-6 trans-signaling, involving shed IL-6 receptor, drives colon cancer and can be blocked by sgp130Fc.

Conclusions:

  • ADAM17-mediated cleavage and subsequent IL-6 trans-signaling are crucial for colon cancer development.
  • Inhibiting IL-6 trans-signaling presents a viable therapeutic strategy for colon cancer.
  • This pathway blockade may also be effective for other EGF-R-related neoplastic diseases.
Keywords:
ADAM17colon cancerepidermal growth factor receptor (EGF-R)inflammation associated cancerinterleukin-6lung cancermetalloproteasesheddingtrans-signalingtumor necrosis factor alpha (TNFα)

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