Research Papers:

Overexpression of IFN-induced protein with tetratricopeptide repeats 3 (IFIT3) in pancreatic cancer: cellular “pseudoinflammation” contributing to an aggressive phenotype

Hanno Niess, Peter Camaj, Ruth Mair, Andrea Renner, Yue Zhao, Carsten Jäckel, Peter J. Nelson, Karl-Walter Jauch and Christiane J. Bruns _

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Oncotarget. 2015; 6:3306-3318. https://doi.org/10.18632/oncotarget.2494

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Hanno Niess1, Peter Camaj2, Ruth Mair1, Andrea Renner1, Yue Zhao1, Carsten Jäckel3, Peter J. Nelson3, Karl-Walter Jauch1 and Christiane J. Bruns2

1 Department of Surgery, Medical Center of the Ludwig-Maximilians-University, Campus Grosshadern, Munich, Germany

2 Department of Surgery, Medical Center of the Otto-von-Guericke-University, Magdeburg, Germany

3 Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universitaet Muenchen, Arbeitsgruppe Klinische Biochemie, Munich, Germany


Christiane J. Bruns, email:

Keywords: IFIT, IFIT3, RIG-G, ISG60, SOX9, inflammation, pancreatic cancer, chemotherapy resistance, cytokine expression

Received: August 12, 2014 Accepted: September 16, 2014 Published: September 17, 2014


Inflammation contributes to important traits that cancer cells acquire during malignant progression. Gene array data recently identified upregulation of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in aggressive pancreatic cancer cells. IFIT3 belongs to the group of interferon stimulated genes (ISG), can be induced by several cellular stress stimuli and by its tetratricopeptide repeats interacts with a multitude of cellular proteins.

Upregulation of IFIT3 was confirmed in the aggressive pancreatic cancer cell line L3.6pl compared with its less aggressive cell line of origin, COLO357FG. Transgenic induction of IFIT3 expression in COLO357FG resulted in greater mass of orthotopic tumors and higher prevalence of metastases. Several important traits that mediate malignancy were altered by IFIT3: increased VEGF and IL-6 secretion, chemoresistance and decreased starvation-induced apoptosis. IFIT3 showed binding to JNK and STAT1, the latter being an important inducer of IFIT3 expression. Despite still being alterable by “classical” IFN or NFκB signaling, our findings indicate constitutive - possibly auto-regulated - upregulation of IFIT3 in L3.6pl without presence of an adequate inflammatory stimulus. The transcription factor SOX9, which is linked to regulation of hypoxia-related genes, was identified as a key mediator of upregulation of the oncogene IFIT3 and thereby sustaining a “pseudoinflammatory” cellular condition.

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