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[B. Cell Biology/Stem Cell] B-20

SOCS3 regulates NOD2 by UPS system in lung cancer

tumorigenesis

In-ho Jeong¹, Sang In Park¹, Peter C. W. Lee¹*

¹Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505,

Korea

SOCS (suppressor of cytokine signaling) protein regulates proliferation, maturation and apoptosis of various cell

types via two distinct mechanisms: directly inhibiting the catalytic activity of Janus Kinases that initiate the
intracellular signaling cascade and catalyzing the ubiquitination of signaling components by recruiting components

of a Cullin5 E3 complex. A few studies demonstrated that SOCS promote tumor progression in several cancers, but
the role of the SOCS and Cullin5 E3 complex in onset of lung cancer has not been evaluated well. In this study, we

identified protein expression level of SOCS3, one of the SOCS box proteins, was frequently higher in tumor tissues
than adjacent normal tissues. Similarly, overexpression of SOCS3 promoted proliferation, migration and invasion

capacity of lung cancer cells. Next, we found that SOCS3 interacts with NOD2 (nucleotide binding oligomerization
domain 2) and ubiquitinates NOD2 directly. Furthermore, lung cancer tissues with higher SOCS3 expression showed

lower NOD2 expression. Truly, overexpression of NOD2 leads to reduced tumorigenicity of lung cancer cells, and
these effects occurred through p38 MAPK and NF-κB pathway. Collectively, our work reveals novel roles of SOCS3

in lung tumorigenesis and proposes SOCS3 as a promising biomarker candidate for therapeutic and diagnostic
target for lung cancer.