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S100A8-Mediated Inflammatory Signaling Drives Colorectal Cancer Progression via the CXCL5/CXCR2 Axis

  • 0Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Journal of Cancer +

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May 31, 2024

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May 31, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

High S100A8/S100A9 expression in colorectal cancer cells promotes inflammation and cancer progression. This study reveals S100A8/S100A9 enhances cytokine secretion and activates pathways driving tumor growth and metastasis.

Area Of Science

  • Oncology
  • Immunology
  • Molecular Biology

Background

  • S100A8/S100A9 proteins are implicated in chronic inflammation and cancer progression.
  • Their extracellular forms modulate metabolism, inflammation, and cancer metastasis via RAGE, TLR4, STAT3, and NF-κB pathways.
  • High S100A8/S100A9 expression in colorectal cancer (CRC) requires further functional elucidation.

Purpose Of The Study

  • To investigate the role of S100A8/S100A9 in colorectal cancer progression.
  • To analyze S100A8/S100A9 expression in CRC tissues and cell lines.
  • To determine the functional impact of S100A8/S100A9 overexpression on CRC cell behavior and signaling.

Main Methods

  • Immunohistochemistry and database analysis (GEO, TCGA) for S100A8/S100A9 expression.
  • In vitro transfection models for S100A8/S100A9 overexpression in colon cancer cells.
  • Cytokine profiling (ELISA, qPCR), pathway analysis (STAT3, NF-κB, ERK-MAPK), and functional assays (MTT, Transwell).
  • In vivo tumorigenesis assays (tail vein, subcutaneous).

Main Results

  • S100A8/S100A9 expression is significantly elevated in CRC epithelial cells versus normal tissues.
  • Overexpression increased secretion of CXCL5, CXCL11, GM-CSF, G-CSF, IL1a, IL1b, sTNF RI, and CCL3, activating STAT3, NF-κB, and ERK-MAPK pathways.
  • S100A8/S100A9 overexpression promoted colon cancer cell proliferation and invasion, reversible by pathway inhibitors and CXCR2 inhibition.
  • In vivo assays confirmed enhanced proliferation and migration.

Conclusions

  • Elevated S100A8/S100A9 in colon cancer cells drives inflammation via NF-κB and ERK-MAPK signaling.
  • S100A8 promotes CRC cell proliferation, invasion, and metastasis, partly through the CXCL5/CXCR2 axis.
  • Targeting S100A8/S100A9 or associated pathways may offer therapeutic strategies for CRC.

Keywords:

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