Phosphorylated ezrin is associated with EBV latent membrane protein 1 in nasopharyngeal carcinoma and induces cell migration
| Autor: | Yoh Zen, Satoru Kondo, Toshiyuki Horikawa, Noriko Kitagawa, Joseph S. Pagano, Kazuhira Endo, Julia Shackleford, Mitsuru Furukawa, Tomokazu Yoshizaki |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
cell migration Nasopharyngeal neoplasm Ezrin macromolecular substances environment and public health Article Viral Matrix Proteins Cytosol Cell Movement Cell Line Tumor Genetics otorhinolaryngologic diseases Humans Neoplasm Invasiveness Phosphorylation Molecular Biology Protein Kinase C Protein kinase C rho-Associated Kinases latent membrane protein 1 biology Kinase nasopharyngeal carcinoma Cell Membrane CD44 Nasopharyngeal Neoplasms Cell migration Transport protein DNA-Binding Proteins Cytoskeletal Proteins Protein Transport stomatognathic diseases Hyaluronan Receptors biology.protein Cancer research Transcription Factors |
| Zdroj: | Oncogene |
| DOI: | 10.17615/5a0x-v806 |
| Popis: | Tumor metastasis is a complex phenomenon that is the culmination of effects of numerous cellular factors. We have shown that the Epstein-Barr virus (EBV) oncoprotein, latent membrane protein 1 (LMP1), is capable of inducing a wide range of such factors in cell culture, expression of which is also elevated in the LMP1-expressing tumor, nasopharyngeal carcinoma (NPC), a highly invasive neoplasm. Recently, the membrane crosslinker protein, ezrin, has been implicated in tumor cell metastasis and malignant progression. In this study, we evaluated the possible role of LMP1 and ezrin in the pathophysiology of NPC. We show that C-terminal phosphorylation of ezrin is increased by the expression of LMP1 in nasopharyngeal (NP) cells through a protein kinase C (PKC) pathway. LMP1 enhances the organization of a ternary complex of CD44, ezrin and F-actin, which is a prerequisite for ezrin phosphorylation. In NPC tissues, the expression of phosphoezrin and LMP1 is directly correlated. Silencing of endogenously expressed ezrin suppresses LMP1-induced cell motility and invasiveness. Moreover, the inhibition of ezrin phosphorylation by PKC inhibitor suppresses migration and invasion of NP cells. These data show that the phosphorylation of ezrin and its recruitment to the cell membrane linked to F-actin and CD44 is a process required for LMP1-stimulated cell motility and invasion of NP cells. |
| Databáze: | OpenAIRE |
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