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

Catanzaro, J. M., Sheshadri, N., Pan, J. A., Sun, Y., Shi, C., Li, J., Powers, R. S., Crawford, H. C., Zong, W. X. (April 2014) Oncogenic Ras induces inflammatory cytokine production by upregulating the squamous cell carcinoma antigens SerpinB3/B4. Nature Communications, 5. p. 3729. ISSN 20411723

URL: http://www.ncbi.nlm.nih.gov/pubmed/24759783
DOI: 10.1038/ncomms4729

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-kappaB 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.

Item Type: Paper
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > oncogene
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > G protein > Ras
CSHL Authors:
Communities: CSHL labs > Powers lab
CSHL Cancer Center Program > Cancer Genetics
Depositing User: Matt Covey
Date: 23 April 2014
Date Deposited: 02 May 2014 18:59
Last Modified: 01 Mar 2016 15:29
PMCID: PMC4025922
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29947

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