The Role Of HMGB1 Regulating P120-catenin/MMP7 Signaling Pathway In Colon Cancer

I.Objective The purpose of this study is to detect the expression and relationship of HMGB1,MMP7 and p120-catenin,and to prove that HMGB1 may promote invasion and metastasis of colon cancer through increased MMP7 expression via downregulating p120-catenin.II.Methods In this study,the expression and distribution of HMGB1,p120-catenin and MMP7 in 80 cases of colon cancer tissue and 42 cases of adjacent normal colon tissue was evaluated by immunohistochemistry;the expression of HMGB1,p120-catenin and MMP7 in colon cancer tissues and adjacent normal colon tissue was also determined by Western blot.Lo Vo cells,an immortalized aggressive human colon cancer cell line,were treated with recombinant human HMGB1.After HMGB1 treatment or pre-transfected with p120 plasmid,the expression of p120-catenin and MMP7 was detected by Western blot.III.Results 1.The expression and relationship of HMGB1,MMP7 and p120-catenin in colon cancer(1)Immunohistochemistry stain showed that the abnormal expression of p120-catenin was related to the size and grading of colon cancer,but not associated with age,gender,TNM staging,lymph node and remote metastasis,Duke and clinical staging of the patients.(2)In colon cancer tissues,p120-catenin membranous expression was reduced(71.25%),but both HMGB1 nuclear expression(88.75%)and MMP7 cytoplasmic expression(86.25%)were increased.And the p120 expression was negatively related with expression of HMGB1 and MMP7.(3)Western blot assay showed: in colon cancer,the expression of HMGB1 and MMP7 was increased,and p120-catenin expression was decreased.2.HMGB1 regulating p120-catenin/ MMP7 singling in Lo Vo cell line(1)After treated with HMGB1 at 80,400,2000ng/ml for 24 hours,the expression of p120-catenin and MMP7 in Lo Vo cells was examined by Western blot.Downregulation of p120 catenin and significant upregulation of MMP7 were found and in a HMGB1 dose-independent manner.(2)Two plasmids of p120-catenin isoform 1A and 3A,were transfected into Lo Vo cells before HMGB1 treatment.Western blot showed that the upregulation of MMP7 was inhibited by overexpression of p120-catenin 1A,the inhibition of p120-catenin 3A was not obvious.IV.Conclusions HMGB1 may promote invasion and metastasis of colon cancer through increased MMP7 expression via downregulating p120-catenin.