CXCL8 Drives MMP1 Upregulation and Promotes Metastatic Progression in Oral Cancer Through CXCR1/2-Mediated JAK1/STAT3

Kuan-Chou Lin1,2, Tsung-Ming Chang3, Ying-Sui Sun3

  • 1School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan.

Abstract

Insights

CXCL8 drives oral cancer metastasis by activating the CXCR1/2-JAK1-STAT3 pathway, leading to MMP1 upregulation. Targeting this pathway may prevent oral squamous cell carcinoma (OSCC) progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metastasis Research

Background:

  • Oral squamous cell carcinoma (OSCC) is an aggressive cancer often diagnosed at advanced stages.
  • Identifying molecular drivers of OSCC metastasis is crucial for effective treatment strategies.
  • CXCL8 is implicated in OSCC progression, but its pro-metastatic mechanisms require clarification.

Purpose of the Study:

  • To elucidate the role of CXCL8 in OSCC metastasis.
  • To identify downstream signaling pathways regulated by CXCL8 in OSCC.
  • To evaluate the therapeutic potential of targeting the CXCL8 pathway in OSCC.

Main Methods:

  • Bioinformatic analysis of GEO datasets to identify upregulated genes in OSCC.
  • In vitro functional assays in OSCC cell lines to assess migration and signaling.
  • Establishment of an orthotopic tongue xenograft mouse model for in vivo validation.

Main Results:

  • CXCL8 expression is significantly upregulated in OSCC tissues and correlates with enhanced cell motility and poor survival.
  • CXCL8 promotes OSCC cell migration via the CXCR1/2-JAK1-STAT3 axis, leading to MMP1 transcriptional upregulation.
  • Inhibition of the CXCL8 pathway components (CXCR1/2, JAK1, STAT3, MMP1) reversed OSCC cell migration and metastasis in vitro and in vivo.

Conclusions:

  • CXCL8 drives OSCC metastasis through CXCR1/2-mediated JAK1/STAT3 activation and subsequent MMP1 upregulation.
  • CXCL8 serves as a prognostic biomarker and a potential therapeutic target for OSCC.
  • Targeting the CXCL8 pathway holds promise for preventing metastatic progression in oral cancer.

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