Ezrin Ser66 phosphorylation regulates invasion and metastasis of esophageal squamous cell carcinoma cells by mediating filopodia formation
| Autor: | Xiu-E Xu, Fa-Min Zeng, Yang-Min Xie, Lian-Di Liao, En-Min Li, Li-Hua Tao, Jian-Jun Xie, Li-Yan Li, Li-Yan Xu, Wen-Ming Xie, Qiang Zhang, Ying-Hua Xie |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Esophageal Neoplasms Carcinogenesis macromolecular substances medicine.disease_cause environment and public health Biochemistry Metastasis 03 medical and health sciences Ezrin Nude mouse Cell Line Tumor medicine Serine Humans Neoplasm Invasiveness Pseudopodia Phosphorylation Cell Proliferation biology Chemistry Cell growth Cell Membrane Cell Biology Actin cytoskeleton biology.organism_classification medicine.disease Cell biology Cytoskeletal Proteins Protein Transport 030104 developmental biology Lymphatic Metastasis Mutation Cancer research Carcinoma Squamous Cell Esophageal Squamous Cell Carcinoma Filopodia |
| Zdroj: | The international journal of biochemistrycell biology. 88 |
| ISSN: | 1878-5875 |
| Popis: | Background Ezrin, links the plasma membrane to the actin cytoskeleton, and plays an important role in the development and progression of human esophageal squamous cell carcinoma (ESCC). However, the roles of ezrin S66 phosphorylation in tumorigenesis of ESCC remain unclear. Methods Distribution of ezrin in membrane and cytosol fractions was examined by analysis of detergent-soluble/-insoluble fractions and cytosol/membrane fractionation. Both immunofluorescence and live imaging were used to explore the role of ezrin S66 phosphorylation in the behavior of ezrin and actin in cell filopodia. Cell proliferation, migration and invasion of ESCC cells were investigated by proliferation and migration assays, respectively. Tumorigenesis, local invasion and metastasis were assessed in a nude mouse model of regional lymph node metastasis. Results Ezrin S66 phosphorylation enhanced the recruitment of ezrin to the membrane in ESCC cells. Additionally, non-phosphorylatable ezrin (S66A) significantly prevented filopodia formation, as well as caused a reduction in the number, length and lifetime of filopodia. Moreover, functional experiments revealed that expression of non-phosphorylatable ezrin (S66A) markedly suppressed migration and invasion but not proliferation of ESCC cells in vitro, and attenuated local invasion and regional lymph node metastasis, but not primary tumor growth of ESCC cells in vivo. Conclusion Ezrin S66 phosphorylation enhances filopodia formation, contributing to the regulation of invasion and metastasis of esophageal squamous cell carcinoma cells. |
| Databáze: | OpenAIRE |
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