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HSP27/IL-6 axis promotes OSCC chemoresistance, invasion and migration by orchestrating macrophages via a positive

Ying Qi1, Juan Cao1, Mingjing Jiang1

  • 1Department of Oral Anatomy and Physiology, Hospital of Stomatology, Jilin Provincial Key Laboratory of Oral Biomedical Engineering, Jilin University, Changchun, 130021, China.

Cell Biology and Toxicology
|January 28, 2025
PubMed

Insights

The HSP27/IL-6 axis fuels oral cancer progression by promoting chemoresistance and invasion. Targeting this axis offers a promising therapeutic strategy for oral squamous cell carcinoma (OSCC) patients.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Tumor-associated macrophages (TAMs) play a critical role in cancer progression.
  • The specific molecular mechanisms driving oral squamous cell carcinoma (OSCC) progression via TAM interactions remain unclear.

Purpose of the Study:

  • To elucidate the molecular mechanism of the HSP27/IL-6 axis in OSCC chemoresistance, invasion, and migration.
  • To investigate the crosstalk between OSCC cells and TAMs mediated by HSP27 and IL-6.

Main Methods:

  • Demonstrated higher HSP27 expression in OSCC cells.
  • Investigated the role of paracrine HSP27 in inducing M2 polarization and IL-6 secretion in TAMs.
  • Analyzed the positive feedback loop between OSCC cells and M2 TAMs involving HSP27 and IL-6.

Main Results:

  • Paracrine HSP27 from OSCC cells enhanced chemoresistance, invasion, migration, and epithelial-mesenchymal transition (EMT) by promoting M2 TAM polarization and IL-6 secretion.
  • A positive feedback loop between HSP27 and IL-6 was established between OSCC cells and M2 TAMs.
  • TAM-derived IL-6 promoted OSCC stemness and chemoresistance via β-catenin and CD44, and enhanced invasion, migration, and EMT through autocrine HSP27/TLR4 signaling.

Conclusions:

  • The HSP27/IL-6 axis facilitates OSCC chemoresistance, invasion, and migration by orchestrating macrophages via a positive feedback loop.
  • Targeting the HSP27/IL-6 axis presents a potential therapeutic strategy for OSCC, aiming to control disease progression and improve patient outcomes.
Keywords:
ChemoresistanceHSP27IL-6MacrophagesOral squamous cell carcinomaTLR4

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