Figure 1. Reciprocal modifications of chloride intracellular channel-4 (CLIC4) in tumor epithelium and stroma directly correlate with tumor progression. A) Immunostaining of CLIC4 in tissue sections from normal colon showing the predominant localization of CLIC4 in nuclei of crypt cells and lamina propria (blue arrows). In contrast, CLIC4 is excluded from tumor epithelium in advanced colon cancer and upregulated in tumor stroma (red arrow) where it is co-expressed with alpha smooth muscle actin (αSMA). B)  Diagram depicting the step-wise reciprocal modifications of CLIC4 (represented by brown color) in epithelial cells and stromal fibroblasts over the course of the multistage development of cancer at multiple organ sites.