| Summary: | 碩士 === 長庚大學 === 醫學生物技術暨檢驗學系 === 99 === N-myc downstream regulated gene 1 (NDRG1) is overexpression in head and neck cancer (HNC) tissues as we reported previously. However, the cellular function of this molecule on tumorigenesis of HNC is still not clear. The three-tandem repeats (3R) of ”GTRSRSHTSE” in the C-terminal region of NDRG1 is a specific feature. NDRG1 is predicted phosphorylated at the serine sites in its 3R motif by glycogen synthase kinase 3 β (GSK3β). In this study, we examined the significance of 3R motif of NDRG1 functions leading to HNCs. Expression of the deletion construct NDRG1ΔC [deletion of 3R motif] suppressed nuclear translocation of NDRG1, and led to significantly reduction of cell migration and invasion in HNC cells. We also observed that SB 216763, an inhibitor of GSK3β decreased the phosphorylation of 3R motif of NDRG1 and attenuated the nuclear translocation, cell migration and invasion. We further introduced mutations at the serine sites at 342 [S342A], 352 [S352A] and 362 [S362A], which are susceptible phosphorylation by GSK3β. Expression of all these mutants repressed NDRG1 nuclear import, cell migration and invasion. Together, these results suggest a novel function by which NDRG1 modulates cell motility and invasion through GSK3β phosphorylated serine sites of 3R motif at serine 342, 352 and 362.
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