Cadherin-12 contributes to tumorigenicity in colorectal cancer by promoting migration, invasion, adhersion and angiogenesis

Abstract

BackgroundCadherin 12 (CDH12), which encodes a type II classical cadherin from the cadherin superfamily, may mediate calcium-dependent cell adhesion. It has been demonstrated that CDH12 could play an important role in the invasion and metastasis of salivary adenoid cystic carcinoma. We decided to investigate the relationship between CDH12 expression level and clinicopathologic variables in colorectal carcinoma (CRC) patients and to explore the functions of CDH12 in tumorigenesis in CRC.MethodsThe expression levels of CDH12 in colorectal carcinoma tissues were detected by immunohistochemistry. Real-time PCR and Western Blot were used to screen CDH12 high-expression cell lines. CCK-8 assay was used to detect the proliferation ability of CRC cells being transfected by shRNAs against CDH12. The wound assay and transwell assay were performed to test migration and invasion ability. The importance of CDH12 in cell-cell junctions was detected by cell adhesion assay and cell aggregation assay. Endothelial tube formation assay was used to test the influence of CDH12 on angiogenesis.ResultsStatistical analysis of clinical cases revealed that the positive rate of CDH12 was higher in the CRC tumor tissues compared with the adjacent non-tumor tissues. The expression levels of CDH12 in CRC patients are significantly correlated with invasion depth. Consistently, the ability of proliferation, migration and invasion were suppressed when CDH12 was decreased in CRC cells transfected with shRNAs. Cell adhesion assay and cell aggregation assay presented that tumor cells tend to disperse with the lack of CDH12. Endothelial tube formation assay showed that down-regulation of CDH12 could obviously inhibit the process of angiogenesis, implying that CDH12 may play an important role in tumor metastasisConclusionOur results showed that CDH12 promotes proliferation, migration, invasion, adhesion and angiogenesis, suggesting that CDH12 may be an oncogene in colorectal cancer. CDH12 is expected to become a new diagnostic and prognostic marker and a novel target of the treatment of colorectal cancer.

Combination Therapy with Quercetin and 5-Fluorouracil Ameliorates 1,2-Dimethylhydrazine Induced Carcinogenesis in the Colon of Wistar Rats.

“…The upregulation of CDH12 protein following DMH administration with the development of ACF is consistent with the fact that CDH12 promotes proliferation and tumorigenesis [46,47]. This In support, SOX7 over-expression suppressed cell proliferation and colony formation in prostate and CRC cell lines and induced apoptosis in CRC cells [49,50].…”

Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3β/β-catenin pathways

“…When cancer cells escape from the primary site to metastasis, subsets of cancer cells undergo a morphological conversion from an epithelial-like phenotype to a mesenchyme-like phenotype [25]. This process is characterized by the loss of epithelial cell junction proteins, such as E-cadherin, and an upregulation of mesenchymal markers, such as Vimentin and N-cadherin [26]. In this study, we found that CRC cells with high levels of CXCL5 expressed low levels of E-cadherin and ZO-1 and high levels of N-cadherin and Vimentin.…”

CCR4 promotes metastasis via ERK/NF-κB/MMP13 pathway and acts downstream of TNF-α in colorectal cancer

“…Western blot analysis was performed as previously described [35]. 100 ug of protein was separated by 10% SDS-PAGE gel and transferred to PVDF membranes.…”