Epigenetic silencing of the 14-3-3σ gene by CpG hypermethylation has been reported in many kinds of cancers, but has been considered inapplicable in the colorectal variety. The expression of 14-3-3σ in colorectal cancer is located primarily in the invasive area. The interaction between tumor cells and the extracellular matrix (ECM) is involved in tumor invasion. In the current study, we investigated the correlation between 14-3-3σ expression and the ECM, focusing especially on the presence of tenascin-C (TNC) at the invasive area of colorectal cancers. Correlations between the immunohistochemical expression of 14-3-3σ and TNC, as well as other clinicopathological factors, were evaluated in 123 colorectal carcinoma tissues. 14-3-3σ expression was frequently observed in budding tumor cells in the invasive area and expression was significantly correlated with budding formation (p=0.001), pTNM classification (p=0.001) and stromal TNC expression (p=0.004). Using colorectal cancer cell lines and ECMs, the up-regulation of 14-3-3σ mRNA levels was investigated by semi-quantitative RT-PCR. TNC surrounding the tumor cells increased 14-3-3σ mRNA expression 1.8- to 2.2-fold in HCT116 cells. The effect of 14-3-3σ over-expression on tumor cell migration was investigated using an agarose-cell droplet migration assay. Over-expression of 14-3-3σ up-regulated HCT116 cell migration on TNC (p<0.001). We concluded that the expression of 14-3-3σ in the invasive area modulates tumor cell migration in certain types of colorectal cancer and thus facilitates tumor progression.

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