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


CONCLUSIONS
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.
Jingkun
J
Zhao
Pu
P
Li
Hao
H
Feng
Puxiongzhi
P
Wang
Yaping
Y
Zong
Junjun
J
Ma
Zhuo
Z
Zhang
Xuehua
X
Chen
Minhua
M
Zheng
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. zhuzg@shsmu.edu.cn.
Zhenggang
Z
Zhu
Aiguo
A
Lu
D000368:Aged; D001483:Base Sequence; D015153:Blotting, Western; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000502:physiology*; D002448:Cell Adhesion; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000473:pathology*; D017931:DNA Primers; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D020133:Reverse Transcriptase Polymerase Chain Reaction
C442480:CDH23 protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; D017931:DNA Primers