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Oncogenic Ras induces inflammatory cytokine production by upregulating the squamous cell carcinoma antigens SerpinB3/B4

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Listed:
  • Joseph M. Catanzaro

    (Stony Brook University)

  • Namratha Sheshadri

    (Stony Brook University)

  • Ji-An Pan

    (Stony Brook University)

  • Yu Sun

    (Stony Brook University)

  • Chanjuan Shi

    (Microbiology and Immunology, Vanderbilt University)

  • Jinyu Li

    (Cancer Genome Center, Cold Spring Harbor Laboratory)

  • R. Scott Powers

    (Cancer Genome Center, Cold Spring Harbor Laboratory)

  • Howard C. Crawford

    (Mayo Clinic)

  • Wei-Xing Zong

    (Stony Brook University)

Abstract

Mounting evidence indicates that oncogenic Ras can modulate cell autonomous inflammatory cytokine production, although the underlying mechanism remains unclear. Here we show that squamous cell carcinoma antigens 1 and 2 (SCCA1/2), members of the Serpin family of serine/cysteine protease inhibitors, are transcriptionally upregulated by oncogenic Ras via MAPK and the ETS family transcription factor PEA3. Increased SCCA expression leads to inhibition of protein turnover, unfolded protein response, activation of NF-κB and is essential for Ras-mediated cytokine production and tumour growth. Analysis of human colorectal and pancreatic tumour samples reveals a positive correlation between Ras mutation, enhanced SCCA expression and IL-6 expression. These results indicate that SCCA is a Ras-responsive factor that plays an important role in Ras-associated cytokine production and tumorigenesis.

Suggested Citation

  • Joseph M. Catanzaro & Namratha Sheshadri & Ji-An Pan & Yu Sun & Chanjuan Shi & Jinyu Li & R. Scott Powers & Howard C. Crawford & Wei-Xing Zong, 2014. "Oncogenic Ras induces inflammatory cytokine production by upregulating the squamous cell carcinoma antigens SerpinB3/B4," Nature Communications, Nature, vol. 5(1), pages 1-12, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4729
    DOI: 10.1038/ncomms4729
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