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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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Protein disulfide isomerase a4 promotes lung cancer development via the Stat3 pathway in stromal cells

Tzung-Yan Chen1,2, Chun-Yen Yang1,3, Meng-Ting Yang1

  • 1Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.

Clinical and Translational Medicine
|February 16, 2022
PubMed
Abstract

Insights

Protein disulfide isomerase a4 (Pdia4) promotes lung cancer by affecting the tumor microenvironment and immune cells. Targeting Pdia4 in cancer stroma offers a promising anti-cancer strategy.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Protein disulfide isomerase a4 (Pdia4) is implicated in cancer development by inhibiting apoptosis.
  • The role of Pdia4 in the tumor microenvironment remains largely unknown.

Purpose of the Study:

  • To investigate the role of host Pdia4 in lung cancer development within the tumor microenvironment.
  • To elucidate the mechanisms by which Pdia4 influences stromal cells and immune responses.

Main Methods:

  • Correlation analysis of Pdia4 expression with patient survival.
  • Genetic studies using Pdia4 knockout mice and Rag1 knockout mice.
  • Analysis of immune cell populations and function.
  • Investigation of signaling pathways including Stat3/Vegf.

Main Results:

  • Pdia4 expression negatively correlates with lung cancer patient survival.
  • Host Pdia4 in stromal cells promotes lung cancer development via the cancer stroma.
  • Pdia4 influences T and B lymphocytes, regulating their number and immunosuppressive function.
  • Host Pdia4 stabilizes activated Stat3 in a Thioredoxin-like domain (CGHC)-dependent manner, controlling the Stat3/Vegf pathway.

Conclusions:

  • Host Pdia4 plays a critical role in promoting lung cancer progression through the tumor microenvironment.
  • Targeting Pdia4 in cancer stroma represents a potential therapeutic strategy for anti-cancer interventions.
Keywords:
Pdia4Stat3cancer stromalung cancer

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