Our previous studies have shown that epithelial–mesenchymal transition (EMT) may be involved in the vasculogenic mimicry (VM) formation in hepatocellular carcinoma. Here, we hypothesize that zinc finger E-box binding homeobox 1 (ZEB1) promotes VM formation in colorectal carcinoma (CRC) by inducing EMT. We identified VM in 39 (19.2%) out of 203 CRC patients. The presence of VM was associated with aggressive biological behavior and was an unfavorable prognostic indicator. By immunohistochemical analysis, we found that the VM-positive CRC samples showed increased ZEB1 expression compared with the VM-negative samples and the ZEB1 expression occurred concomitantly with features of EMT. In vitro, knockdown of ZEB1 in poorly differentiated HCT116 CRC cells destroyed the vessel-like structures in the 3-D culture, a property associated with VM formation. Knockdown of ZEB1 resulted in restoration of epithelial phenotypes and significantly inhibited the ability to migrate and invade. In addition, ZEB1 underexpression decreased the expression of vascular endothelial (VE)-cadherin and Flk-1, which are characteristics of endothelial cells. Taken together, our results suggest that ZEB1 can promote VM formation by inducing EMT in CRC and might represent an important target in CRC. (Cancer Sci 2012; 103: 813–820)

Background: The incidence of malignant melanoma (MM) was occurring at a faster rate than for most neoplasm worldwide, and melanoma metastasis is still the most formidable problem. So it is necessarily to find some biomarkers associated with melanoma metastasis. Methods: In our study, 8 spontaneous lung metastatic mice models were created by B16F10 subcutaneously transplantation. The differential protein profiles of two kinds of subcutaneous transplanted tumor tissues, which was parental B16F10 (B16 group) and corresponding lung metastases (B16M group) were detected by two-dimensional differential in-gel electrophoresis (2D-DIGE) combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). Western blotting was used to validate the results, and the clinical significance of individual protein was detected furtherly in a set of human samples. Result: In this study, thirty proteins were found to be differentially expressed (ratio > 2 or < -2, P < 0.01) and thirteen of them were identified by MS. Highly expressed proteins in B16M group included cytoskeleton/structure proteins (vimentin, gamma-actin, β-actin, laminin binding protein), the chaperone family of proteins (heavy-chain binding protein, Bip), immunoproteasome assembly (proteasome activator REG alpha) and others involved in glycolysis activity (PGK1, enolase, TPI, human skeletal muscle GAPDH) and protein transport (myoglobin). Vimentin was significantly up-regulated in B16M group compared with B16 group which was validated by western blotting. Immunohistochemistry was performed in a set of clinical samples, the results showed that over-expression of vimentin was frequently observed in primary melanoma patients with hematogenous metastasis (P < 0.05), not associated with lymph node metastasis (P > 0.05). The presence of TNM stage was a independent indicator of poor prognosis for melanoma patients (P = 0.004). Conclusion: The aberrant immunohistochemical expression of vimentin in primary melanoma tissues may help to call attention for patients with high risk of hematogenous metastasis. That might be as a novel metastatic indicator for melanoma. In a word, vimentin is not only the dignostic marker but also the hematogenous metastasis predictor for melanomas clinically.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) have been widely used for the treatment of non-small cell lung cancer (NSCLC). KRAS and EGFR somatic mutations in NSCLC may predict resistance and responsiveness to TKI, respectively. Nevertheless, most research to date has been conducted on samples from primary tumors. For many patients with advanced disease, their samples can only be obtained from metastases for test. The molecular characteristics of metastasized tumors may be different from those of primary tumors.

This study aimed to determine the expression pattern of dickkopf-1 (Dkk1), a potent inhibitor of Wnt signaling, in colon cancer and to assess the function and mechanism of Dkk1 in tumor progression in vitro and in vivo. We detected the protein expression of Dkk1 and some epithelial-mesenchymal transition (EMT)-associated markers (E-cadherin, vimentin and β-catenin) in 217 tissue samples of human colon cancer, upregulated Dkk1 expression in HCT116 colon cancer cells, and established a nude mouse xenograft model. Dkk1 protein overexpression was inversely related to tumor grade and the presence of metastasis and recurrence of colon cancer. Notably, the expression of Dkk1 was concomitant with reduced immunohistochemical features of EMT (e.g. increased expression of epithelial marker E-cadherin, decreased expression of mesenchymal marker vimentin, and cytoplasmic distribution of β-catenin). Furthermore, Dkk1 overexpression resulted in restoration of the epithelial phenotype, decreased expression of EMT transcription factors Snail and Twist, and decreased expression of markers suggestive of intestinal stem cells (e.g. cluster of differentiation 133 [CD133] and leucine-rich-repeat-containing G-protein-coupled receptor 5 [Lgr5]). Functional analysis showed overexpression of Dkk1 reduced proliferation, migration, and invasion of colon cancer cells. Moreover, upregulation of Dkk1 led to decreased tumor-initiating ability and suppressed colon tumor growth in nude mice. Our findings indicate that Dkk1 can suppress the progression of colon cancer, possibly through EMT inhibition, and could therefore serve as a target for tumor therapy. (Cancer Sci 2012; 103: 828–835)