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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kang, Minkyung Lee, Jung Weon Kim, Hye-jin Choi, Yoon-ju Ryu, Jihye Kwak, Tae Kyoung Jung, Oisun Lee, Mi-sook |
| Description | Author Affiliation: Jung O ( Interdisciplinary Program in Genetic Engineering, Seoul National University, Seoul 151-742, Republic of Korea.) |
| 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 $_{ΔC}$ cells were more efficient than WT TM4SF5 cells, suggesting a negative regulatory role by the C-terminus. TM4SF5 WT- or TM4SF5 $_{ΔC}$ -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 $_{ΔC}$ -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. |
| ISSN | 00063002 |
| Journal | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer |
| Issue Number | 3 |
| Volume Number | 1833 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2013-03-01 |
| Publisher Place | Netherlands |
| Access Restriction | Open |
| Subject Keyword | Carcinoma, Hepatocellular Pathology Cell Movement Liver Neoplasms Membrane Proteins Metabolism Proto-Oncogene Proteins Pp60(c-src) Receptor, Epidermal Growth Factor Tyrosine Blotting, Western Genetics Cell Adhesion Cell Proliferation Fluorescent Antibody Technique Immunoprecipitation Neoplasm Invasiveness Phosphorylation Protein Structure, Tertiary RNA, Messenger Signal Transduction Tumor Cells, Cultured Research Support, Non-U.S. Gov't Biochemistry |
| Content Type | Text |
| Resource Type | Article |
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