Skip to main content
Top
Published in: Journal of Translational Medicine 1/2013

Open Access 01-12-2013 | Research

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

Authors: Jingkun Zhao, Pu Li, Hao Feng, Puxiongzhi Wang, Yaping Zong, Junjun Ma, Zhuo Zhang, Xuehua Chen, Minhua Zheng, Zhenggang Zhu, Aiguo Lu

Published in: Journal of Translational Medicine | Issue 1/2013

Login to get access

Abstract

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Gumbiner BM: Cell adhesion: the molecular basis of tissue architecture and morphogenesis. Cell. 1996, 84: 345-357. 10.1016/S0092-8674(00)81279-9.CrossRefPubMed Gumbiner BM: Cell adhesion: the molecular basis of tissue architecture and morphogenesis. Cell. 1996, 84: 345-357. 10.1016/S0092-8674(00)81279-9.CrossRefPubMed
2.
go back to reference Li K, He W, Lin N, Wang X, Fan QX: Downregulation of N-cadherin expression inhibits invasiveness, arrests cell cycle and induces cell apoptosis in esophageal squamous cell carcinoma. Cancer Invest. 2010, 28: 479-486. 10.3109/07357900903476745.CrossRefPubMed Li K, He W, Lin N, Wang X, Fan QX: Downregulation of N-cadherin expression inhibits invasiveness, arrests cell cycle and induces cell apoptosis in esophageal squamous cell carcinoma. Cancer Invest. 2010, 28: 479-486. 10.3109/07357900903476745.CrossRefPubMed
3.
go back to reference Yang Z, Zhang X, Gang H, Li X, Li Z, Wang T, Han J, Luo T, Wen F, Wu X: Up-regulation of gastric cancer cell invasion by Twist is accompanied by N-cadherin and fibronectin expression. Biochem Biophys Res Commun. 2007, 358: 925-930. 10.1016/j.bbrc.2007.05.023.CrossRefPubMed Yang Z, Zhang X, Gang H, Li X, Li Z, Wang T, Han J, Luo T, Wen F, Wu X: Up-regulation of gastric cancer cell invasion by Twist is accompanied by N-cadherin and fibronectin expression. Biochem Biophys Res Commun. 2007, 358: 925-930. 10.1016/j.bbrc.2007.05.023.CrossRefPubMed
4.
go back to reference Hulit J, Suyama K, Chung S, Keren R, Agiostratidou G, Shan W, Dong X, Williams TM, Lisanti MP, Knudsen K, Hazan RB: N-cadherin signaling potentiates mammary tumor metastasis via enhanced extracellular signal-regulated kinase activation. Cancer Res. 2007, 67: 3106-3116. 10.1158/0008-5472.CAN-06-3401.CrossRefPubMed Hulit J, Suyama K, Chung S, Keren R, Agiostratidou G, Shan W, Dong X, Williams TM, Lisanti MP, Knudsen K, Hazan RB: N-cadherin signaling potentiates mammary tumor metastasis via enhanced extracellular signal-regulated kinase activation. Cancer Res. 2007, 67: 3106-3116. 10.1158/0008-5472.CAN-06-3401.CrossRefPubMed
5.
go back to reference Alexander NR, Tran NL, Rekapally H, Summers CE, Glackin C, Heimark RL: N-cadherin gene expression in prostate carcinoma is modulated by integrin-dependent nuclear translocation of Twist1. Cancer Res. 2006, 66: 3365-3369. 10.1158/0008-5472.CAN-05-3401.CrossRefPubMed Alexander NR, Tran NL, Rekapally H, Summers CE, Glackin C, Heimark RL: N-cadherin gene expression in prostate carcinoma is modulated by integrin-dependent nuclear translocation of Twist1. Cancer Res. 2006, 66: 3365-3369. 10.1158/0008-5472.CAN-05-3401.CrossRefPubMed
6.
go back to reference Wheelock MJ, Shintani Y, Maeda M, Fukumoto Y, Johnson KR: Cadherin switching. J Cell Sci. 2008, 121: 727-735. 10.1242/jcs.000455.CrossRefPubMed Wheelock MJ, Shintani Y, Maeda M, Fukumoto Y, Johnson KR: Cadherin switching. J Cell Sci. 2008, 121: 727-735. 10.1242/jcs.000455.CrossRefPubMed
7.
go back to reference Center MM, Jemal A, Ward E: International trends in colorectal cancer incidence rates. Cancer Epidemiol Biomarkers Prev. 2009, 18: 1688-1694. 10.1158/1055-9965.EPI-09-0090.CrossRefPubMed Center MM, Jemal A, Ward E: International trends in colorectal cancer incidence rates. Cancer Epidemiol Biomarkers Prev. 2009, 18: 1688-1694. 10.1158/1055-9965.EPI-09-0090.CrossRefPubMed
8.
go back to reference Redies C, Hertel N, Hubner CA: Cadherins and neuropsychiatric disorders. Brain Res. 2012, 1470: 130-144.CrossRefPubMed Redies C, Hertel N, Hubner CA: Cadherins and neuropsychiatric disorders. Brain Res. 2012, 1470: 130-144.CrossRefPubMed
9.
go back to reference Mayer M, Bercsenyi K, Geczi K, Szabo G, Lele Z: Expression of two type II cadherins, Cdh12 and Cdh22 in the developing and adult mouse brain. Gene Expr Patterns. 2010, 10: 351-360. 10.1016/j.gep.2010.08.002.CrossRefPubMed Mayer M, Bercsenyi K, Geczi K, Szabo G, Lele Z: Expression of two type II cadherins, Cdh12 and Cdh22 in the developing and adult mouse brain. Gene Expr Patterns. 2010, 10: 351-360. 10.1016/j.gep.2010.08.002.CrossRefPubMed
10.
go back to reference Bankovic J, Stojsic J, Jovanovic D, Andjelkovic T, Milinkovic V, Ruzdijic S, Tanic N: Identification of genes associated with non-small-cell lung cancer promotion and progression. Lung Cancer. 2010, 67: 151-159. 10.1016/j.lungcan.2009.04.010.CrossRefPubMed Bankovic J, Stojsic J, Jovanovic D, Andjelkovic T, Milinkovic V, Ruzdijic S, Tanic N: Identification of genes associated with non-small-cell lung cancer promotion and progression. Lung Cancer. 2010, 67: 151-159. 10.1016/j.lungcan.2009.04.010.CrossRefPubMed
11.
go back to reference Wang JF, She L, Su BH, Ding LC, Zheng FF, Zheng DL, Lu YG: CDH12 promotes the invasion of salivary adenoid cystic carcinoma. Oncol Rep. 2011, 26: 101-108.PubMed Wang JF, She L, Su BH, Ding LC, Zheng FF, Zheng DL, Lu YG: CDH12 promotes the invasion of salivary adenoid cystic carcinoma. Oncol Rep. 2011, 26: 101-108.PubMed
12.
go back to reference Hu H, Krasinskas A, Willis J: Perspectives on current tumor-node-metastasis (TNM) staging of cancers of the colon and rectum. Semin Oncol. 2011, 38: 500-510. 10.1053/j.seminoncol.2011.05.004.CrossRefPubMed Hu H, Krasinskas A, Willis J: Perspectives on current tumor-node-metastasis (TNM) staging of cancers of the colon and rectum. Semin Oncol. 2011, 38: 500-510. 10.1053/j.seminoncol.2011.05.004.CrossRefPubMed
13.
go back to reference Shimazui T, Kojima T, Onozawa M, Suzuki M, Asano T, Akaza H: Expression profile of N-cadherin differs from other classical cadherins as a prognostic marker in renal cell carcinoma. Oncol Rep. 2006, 15: 1181-1184.PubMed Shimazui T, Kojima T, Onozawa M, Suzuki M, Asano T, Akaza H: Expression profile of N-cadherin differs from other classical cadherins as a prognostic marker in renal cell carcinoma. Oncol Rep. 2006, 15: 1181-1184.PubMed
14.
go back to reference Zhan DQ, Wei S, Liu C, Liang BY, Ji GB, Chen XP, Xiong M, Huang ZY: Reduced N-cadherin expression is associated with metastatic potential and poor surgical outcomes of hepatocellular carcinoma. J Gastroenterol Hepatol. 2012, 27: 173-180. 10.1111/j.1440-1746.2011.06847.x.CrossRefPubMed Zhan DQ, Wei S, Liu C, Liang BY, Ji GB, Chen XP, Xiong M, Huang ZY: Reduced N-cadherin expression is associated with metastatic potential and poor surgical outcomes of hepatocellular carcinoma. J Gastroenterol Hepatol. 2012, 27: 173-180. 10.1111/j.1440-1746.2011.06847.x.CrossRefPubMed
15.
go back to reference Li P, Lin Y, Zhang Y, Zhu Z, Huo K: SSX2IP promotes metastasis and chemotherapeutic resistance of hepatocellular carcinoma. J Transl Med. 2013, 11: 52-10.1186/1479-5876-11-52.PubMedCentralCrossRefPubMed Li P, Lin Y, Zhang Y, Zhu Z, Huo K: SSX2IP promotes metastasis and chemotherapeutic resistance of hepatocellular carcinoma. J Transl Med. 2013, 11: 52-10.1186/1479-5876-11-52.PubMedCentralCrossRefPubMed
16.
go back to reference Li P, Chen X, Su L, Li C, Zhi Q, Yu B, Sheng H, Wang J, Feng R, Cai Q: Epigenetic silencing of miR-338-3p contributes to tumorigenicity in gastric cancer by targeting SSX2IP. PLoS One. 2013, 8: e66782-10.1371/journal.pone.0066782.PubMedCentralCrossRefPubMed Li P, Chen X, Su L, Li C, Zhi Q, Yu B, Sheng H, Wang J, Feng R, Cai Q: Epigenetic silencing of miR-338-3p contributes to tumorigenicity in gastric cancer by targeting SSX2IP. PLoS One. 2013, 8: e66782-10.1371/journal.pone.0066782.PubMedCentralCrossRefPubMed
17.
go back to reference Mirshahi P, Rafii A, Vincent L, Berthaut A, Varin R, Kalantar G, Marzac C, Calandini OA, Marie JP, Soria C: Vasculogenic mimicry of acute leukemic bone marrow stromal cells. Leukemia. 2009, 23: 1039-1048. 10.1038/leu.2009.10.CrossRefPubMed Mirshahi P, Rafii A, Vincent L, Berthaut A, Varin R, Kalantar G, Marzac C, Calandini OA, Marie JP, Soria C: Vasculogenic mimicry of acute leukemic bone marrow stromal cells. Leukemia. 2009, 23: 1039-1048. 10.1038/leu.2009.10.CrossRefPubMed
18.
go back to reference Natalwala A, Spychal R, Tselepis C: Epithelial-mesenchymal transition mediated tumourigenesis in the gastrointestinal tract. World J Gastroenterol. 2008, 14: 3792-3797. 10.3748/wjg.14.3792.PubMedCentralCrossRefPubMed Natalwala A, Spychal R, Tselepis C: Epithelial-mesenchymal transition mediated tumourigenesis in the gastrointestinal tract. World J Gastroenterol. 2008, 14: 3792-3797. 10.3748/wjg.14.3792.PubMedCentralCrossRefPubMed
19.
20.
go back to reference Hanahan D, Weinberg RA: Hallmarks of cancer: the next generation. Cell. 2011, 144: 646-674. 10.1016/j.cell.2011.02.013.CrossRefPubMed Hanahan D, Weinberg RA: Hallmarks of cancer: the next generation. Cell. 2011, 144: 646-674. 10.1016/j.cell.2011.02.013.CrossRefPubMed
Metadata
Title
Cadherin-12 contributes to tumorigenicity in colorectal cancer by promoting migration, invasion, adhersion and angiogenesis
Authors
Jingkun Zhao
Pu Li
Hao Feng
Puxiongzhi Wang
Yaping Zong
Junjun Ma
Zhuo Zhang
Xuehua Chen
Minhua Zheng
Zhenggang Zhu
Aiguo Lu
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2013
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-11-288

Other articles of this Issue 1/2013

Journal of Translational Medicine 1/2013 Go to the issue