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The COOH-terminus of TM4SF5 in hepatoma cell lines regulates c-Src to form invasive protrusions via EGFR Tyr845 phosphorylation

Cited 25 time in Web of Science Cited 26 time in Scopus
Authors

Jung, Oisun; Choi, Yoon-Ju; Kwak, Tae Kyoung; Kang, Minkyung; Lee, Mi-Sook; Ryu, Jihye; Kim, Hye-Jin; Lee, Jung Weon

Issue Date
2013-03
Publisher
Elsevier BV
Citation
Biochimica et Biophysica Acta - Molecular Cell Research, Vol.1833 No.3, pp.629-642
Abstract
Transmembrane 4 L six family member 5 (TM4SF5) enhances cell migration and invasion, although how TM4SF5 mechanistically mediates these effects remains unknown. In the study, during efforts to understand TM4SF5-mediated signal transduction, TM4SF5 was shown to bind c-Src and thus hepatoma cell lines expressing TM4SF5 were analyzed for the significance of the interaction in cell invasion. The C-terminus of TM4SF5 bound both inactive c-Src that might be sequestered to certain cellular areas and active c-Src that might form invasive protrusions. Wildtype (WT) TM4SF5 expression enhanced migration and invasive protrusion formation in a c-Src-dependent manner, compared with TM4SF5-null control hepatoma cell lines. However, tailless TM4SF5(Delta C) cells were more efficient than WTTM4SF5 cells, suggesting a negative regulatory role by the C-terminus. TM4SF5 WT- or TM4SF5(Delta C)-mediated formation of invasive protrusions was dependent or independent on serum or epidermal growth factor treatment, respectively, although they both were dependent on c-Src. The c-Src activity of TM4SF5 WT- or TM4SF5(Delta C)-expressing cells correlated with enhanced Tyr845 phosphorylation of epidermal growth factor receptor. Y845F EGFR mutation abolished the TM4SF5-mediated invasive protrusions, but not c-Src phosphorylation. Our findings demonstrate that TM4SF5 modulates c-Src activity during TM4SF5-mediated invasion through a TM4SF5/c-Src/EGFR signaling pathway, differentially along the leading protrusive edges of an invasive cancer cell. (C) 2012 Elsevier B.V. All rights reserved.
ISSN
0167-4889
Language
English
URI
https://hdl.handle.net/10371/82072
DOI
https://doi.org/10.1016/j.bbamcr.2012.11.026
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