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Cross-talk between the TM4SF5/FAK and the IL6/STAT3 pathways renders immune escape of human liver cancer cells

Cited 14 time in Web of Science Cited 15 time in Scopus
Authors
Ryu, Jihye; Kang, Minkyung; Lee, Mi-Sook; Kim, Hye-Jin; Nam, Seo Hee; Song, Haeng Eun; Lee, Doohyung; Lee, Jung Weon
Issue Date
2014-08
Publisher
American Society for Microbiology
Citation
Molecular and Cellular Biology, Vol.34 No.16, pp. 2946-2960
Keywords
복합학FAKIL6invasionSTAT3immune escape
Abstract
TM4SF5 overexpressed in hepatocellular carcinoma activates FAK during tumor cell migration. However, it remains unknown how TM4SF5 in hepatocellular carcinoma cells compromise with immune actions initiated by extracellular cytokines. Normal and cancerous hepatocytes with or without TM4SF5 expression were analyzed for the effects of cytokine signaling activity on TM4SF5/FAK signaling and metastatic potential. We found that IL6 was differentially expressed in hepatocytes depending on cancerous malignancy and TM4SF5 expression. IL6 treatment activated FAK and STAT3 and enhanced focal adhesion (FA) formation in TM4SF5-null cells, but it decreased TM4SF6-dependent FAK activity and FAformation in SNU761-TM4SF5 cells. STAT3 suppression abolished the IL6-mediated effects in normal Chang cells, but it did not recover the TM4SF5-dependent FAK activity that was inhibited by IL6 treatment in cancerous SNU761-TM4SF5 cells. In addition, modulation of FAK activity did not change the IL6-mediated STAT3 activity in either the Chang or SNU761 cell system. TM4SF5 expression in SNU761 cells caused invasive extracellular matrix degradation negatively depending on IL6/IL6R signaling. Thus, it is likely that hepatic cancer cells might adopt TM4SF5-dependent FAK activation and metastatic potential by lowering IL6 expression and thus avoiding its immunological action through the IL6-STAT3pathway.
ISSN
0270-7306
Language
English
DOI
https://doi.org/10.1128/MCB.00660-14

https://doi.org/10.1128/MCB.00660-14
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College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Journal Papers (저널논문_약학과)
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