S100A8 and S100A9 Are Associated with Colorectal Carcinoma Progression and Contribute to Colorectal Carcinoma Cell Survival and Migration via Wnt/β-Catenin Pathway

Background and Objective: S100A8 and S100A9, two members of the S100 protein family, have been reported in association with the tumor cell differentiation and tumor progression. Previous study has showed that their expression in stromal cells of colorectal carcinoma (CRC) is associated with tumor size. Here, we investigated the clinical significances of S100A8 and S100A9 in tumor cells of CRC and their underlying molecular mechanisms. Methods: Expression of S100A8 and S100A9 in colorectal carcinoma and matching distal normal tissues were measured by reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry and western blot. CRC cell lines treated with the recombinant S100A8 and S100A9 proteins were used to analyze the roles and molecular mechanisms of the two proteins in CRC in vitro. Results: S100A8 and S100A9 were elevated in more than 50% of CRC tissues and their expression in tumor cells was associated with differentiation, Dukes stage and lymph node metastasis. The CRC cell lines treatment with recombinant S100A8 and S100A9 proteins promoted the viability and migration of CRC cells. Furthermore, the two recombinant proteins also resulted in the increased levels of beta-catenin and its target genes c-myc and MMP7. beta-catenin over-expression in CRC cells by Ad beta-catenin increased cell viability and migration. beta-catenin knock-down by Adsi beta-catenin reduced cell viability and migration. Furthermore, beta-catenin knockdown also partially abolished the promotive effects of recombinant S100A8 and S100A9 proteins on the viability and migration of CRC cells. Conclusions: Our work demonstrated that S100A8 and S100A9 are linked to the CRC progression, and one of the underlying molecular mechanisms is that extracellular S100A8 and S100A9 proteins contribute to colorectal carcinoma cell survival and migration via Wnt/beta-catenin pathway.