Role of WW domain-containing oxidoreductase in MAPK signaling
| Autor: | Po-ChihHsu, 許博智 |
|---|---|
| Rok vydání: | 2012 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 100 WW domain-containing oxidoreductase (known as WWOX, FOR or WOX1) is encoded by a fragile gene WWOX. Loss of WOX1 protein expression has been shown in many human cancers. It has been suggested that downregulation of WOX1 protein expression is associated with tumorigenesis. Interestingly, we previously found that ectopic expression of WOX1 regulated the prosurvival PI3K/AKT signaling pathway. Our recent data showed that overexpression of WOX1 in SCC-15 cells regulated protein phosphorylation of ERK, a key kinase involved in many cellular functions. Substantial clinical evidences indicated that aberrant ERK signaling is frequently found in cancer cells. Thus, the aim of this study is to investigate the molecular mechanism by which WOX1 regulates ERK signaling pathway. In SCC-15 cells overexpressing WOX1, protein phosphorylation of ERK upstream kinase, MEK was also increased. Consistently, using HeLa tet-on system, our results demonstrated that inducible expression of WOX1 upregulated protein phosphorylation of MEK and ERK. MEK/ERK cascade is the main route of mitogen-activating protein kinase (MAPK) pathway that regulates cell proliferation, differentiation, and survival. MEK inhibitor U0126 significantly blocked WOX1-induced upregulation of ERK phosphorylation. In conclusion, our results suggest that WOX1 activates MEK/ERK pathway. Delineating the functional role of WOX1 in MAPK signaling pathway will provide a novel molecular insight into the influence of WOX1 on cancer progression. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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