Abstract
Cadherin-12 (CDH12) is a subtype of N-cadherin family. In this study, we investigated the expression of CDH12 and the role of CDH12 in prognosis of colorectal cancer (CRC) patients. In addition, we observed the influence of CDH12 on proliferation and progression of CRC cell lines. By using immunohistochemical staining, we analyzed CRC samples and adjacent non-tumor tissues collected from 78 patients who underwent laparoscopic surgery in Shanghai Minimally Invasive Center, China. Statistical analyses were used to analyze relationship between CDH12 and tumor features. Kaplan-Meier method was used to analyze patients’ survival. Proliferation ability of CRC cells was tested by CCK-8 assay, and transwell assays were performed to detect migration and invasion ability. Western blot assay was performed to investigate epithelial-mesenchymal transition (EMT) variants. We found that expression of CDH12 in tumor tissue was higher than in adjacent normal tissue. High expression of CDH12 was associated with tumor invasion depth and predicts poor prognosis of CRC patients. Ectopic/repressing expression of CDH12 increased/decreased the proliferation and migration ability of CRC cells. CDH12 is able to increase cancer cell migration and invasion via promoting EMT by targeting transcriptional factor Snail. These findings may conclude that CDH12 may act as a predictor in CRC patients’ prognosis and an oncogene in CRC cell proliferation and migration. CDH12 may influence CRC cell progression through promoting EMT by targeting Snail. In addition, CDH12 is promoted by MCP1 through induction of MCPIP.Electronic supplementary materialThe online version of this article (doi:10.1007/s13277-015-4555-z) contains supplementary material, which is available to authorized users.
Highlights
Colorectal cancer (CRC) is one of the most prevalent cancer types worldwide and leads to the third death of cancer-related patients
We demonstrated that CDH12 acts as an oncogene in colorectal cancer cell invasion and migration
We performed immunohistochemistry staining in tissue microarray of 78 cases and further found that CDH12 expression was significantly increased in CRC tissues compared to adjacent normal tissue
Summary
Colorectal cancer (CRC) is one of the most prevalent cancer types worldwide and leads to the third death of cancer-related patients. We presented the clinical significance of CDH12 in CRC patients’ specimens and elucidated its preminent influence on colon cancer cell proliferation as well as invasion. We found that CDH12 promotes CRC cell metastasis by promoting EMT via targeting transcriptional factor Snail. Monocyte chemotactic protein 1 (MCP1) is able to modulate CDH12 expression through induction of MCP1-induced protein (MCPIP) These findings may partially reveal possible molecular mechanisms of CDH12 promoting migration and invasion in CRC cells. Western blot analysis was performed as previous description In this experiment, primary antibodies were rabbit polyclonal antiCDH12 antibody (Abcam), 1:100; rabbit polyclonal antiEMT marker antibodies (including E-cadherin, N-cadherin, beta-catenin (β-catenin), Snail, and Slug), 1:1000 ShRNA targeting nonhomologous gene to CDH12 was performed as control.
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