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

Joseph M. Catanzaro, Namratha Sheshadri, Ji-An Pan, Yu Sun, Chanjuan Shi, Jinyu Li, R. Scott Powers, Howard C. Crawford and Wei-Xing Zong ()
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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

Nature Communications, 2014, vol. 5, issue 1, 1-12

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms4729

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