| Objective: To evaluate the expression levels and clinical significance ofNDRG1in colorectal cancer tissues, to investigate novel molecularmechanism of NDRG1in cytoskeleton remodeling and its effects onmigration/invasion of colorectal cancer cells.Methods:(1) NDRG1protein expression levels in240colorectal cancertissue samples collected between January2006and December2007wereevaluated with immunohistochemistry. Calculate the correlation betweenthe expression of NDRG1protein and anatomopathological feature in240colorectal cancer tissue samples, and whether the expression of NDRG1was correlated with patient outcomes.(2)Wound Healing assay andTrasnwell assay were used to detect the influence of NDRG1onmigration ability of CRC cell lines.(3) Analysis the effect of NDRG1onactin filament (F-actin) polymerization by Western Blot.(4) The affect ofNDRG1on expression of PAK1and pMLC2expression was showed by western blot, and IAP3, the PAK1inhibitor, was used to detect theinfluence of PAK1on pMLC2expression.(5) Analysis the correlation ofPAK1expression and NDRG1expression in CRC tissues.Results:(1) NDRG1protein expression decreased in colorectal cancertissues compared with paired non-tumor tissues.(2) NDRG1expressionin colorectal cancer correlates with patientoutcomes,and it can beregarded as a risk factor for CRC patient.(3) Actin filament (F-actin)polymerization was affected by NDRG1expression, which reduced themigration ability of CRC cells.(4) NDRG1inhibited the expression ofpMLC2by activating PAK1expression.(5) The expression of NDRG1inCRC tissues was positively correlated with PAK1expression.Conclusion:(1) NDRG1was a new prognostic biomarker of colorectalcancer cases, espacially for stage II and Stage III patients.(2) NDRG1inhibited colorectal cancer cell cytoskeleton remodeling via mediatingPAK1associated MLC2phosphorylation, which inhibitsmigration/invasion of CRC in vitro and in vivo. |
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