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

Journal of Translational Medicine

Aiguo Lu¹  Zhenggang Zhu¹  Minhua Zheng¹  Xuehua Chen¹  Zhuo Zhang¹  Junjun Ma¹  Yaping Zong¹  Puxiongzhi Wang¹  Hao Feng¹  Pu Li¹  Jingkun Zhao¹ 

[1] Shanghai Minimally Invasive Surgery Center, Shanghai Key Laboratory of Gastric Neoplasms, Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Rui Jin Er Rd, Shanghai 200025, People’s Republic of China

关键词: Angiogenesis;    Cell adhesion;    Cell invasion;    Cell migration;    Cell proliferation;    Colorectal cancer;    Cadherin12;   

Others  :  824555
DOI  :  10.1186/1479-5876-11-288

 received in 2013-05-20, accepted in 2013-10-21,  发布年份 2013

【 摘 要 】

Background

Cadherin 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.

Methods

The 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.

Results

Statistical 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 metastasis

Conclusion

Our 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.

【 授权许可】

   
2013 Zhao et al.; licensee BioMed Central Ltd.

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