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

Cadherin-12 contributes to tumorigenicity in colorectal cancer by promoting migration, invasion, adhersion and angiogenesis.
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Cadherin-12 通过促进迁移、侵袭、粘附和血管生成而导致结直肠癌的致瘤性。

DOI:
10.1186/1479-5876-11-288
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发表时间:
2013-11-15
影响因子:
7.4
通讯作者:
Lu A
Lu A
中科院分区:
医学2区
文献类型:
--
作者:
Zhao J;Li P;Feng H;Wang P;Zong Y;Ma J;Zhang Z;Chen X;Zheng M;Zhu Z;Lu A

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钙粘蛋白12(CDH 12)编码钙粘蛋白超家族的II型经典钙粘蛋白,可介导钙依赖性细胞粘附。研究表明,CDH 12在涎腺腺样囊性癌的侵袭和转移中起重要作用。本研究旨在探讨CDH 12在结直肠癌组织中的表达水平与临床病理因素的关系,并探讨CDH 12在结直肠癌发生发展中的作用。采用免疫组化法检测大肠癌组织中CDH 12的表达水平。采用Real-time PCR和Western Blot方法筛选CDH 12高表达细胞株。CCK-8法检测转染CDH 12 shRNA的大肠癌细胞的增殖能力。采用创伤实验和transwell实验检测细胞的迁移和侵袭能力。通过细胞粘附试验和细胞聚集试验检测CDH 12在细胞连接中的重要性。内皮管形成实验检测CDH 12对血管生成的影响。临床病例统计分析显示,CDH 12在结直肠癌组织中的阳性率高于癌旁组织。CDH 12的表达水平与大肠癌浸润深度密切相关。结论:转染shRNA的大肠癌细胞中,CDH 12表达下调后,其增殖、迁移和侵袭能力受到抑制。细胞粘附实验和细胞聚集实验表明,肿瘤细胞倾向于分散,缺乏CDH 12。内皮管形成实验表明,CDH 12表达下调可明显抑制血管生成,提示CDH 12可能在肿瘤转移中起重要作用。我们的研究结果表明,CDH 12促进细胞增殖、迁移、侵袭、粘附和血管生成,提示CDH 12可能是大肠癌的一个癌基因。CDH 12有望成为结直肠癌新的诊断和预后标志物以及新的治疗靶点。
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. 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. 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 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.
DOI: 10.3892/or.2011.1286
发表时间: 2011-07-01
期刊: ONCOLOGY REPORTS
影响因子: 4.2
作者:
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DOI: 10.1158/0008-5472.can-05-3401
发表时间: 2006-04-01
期刊: CANCER RESEARCH
影响因子: 11.2
作者:
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DOI: 10.3109/07357900903476745
发表时间: 2010-06-01
影响因子: 2.4
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Twist 上调胃癌细胞侵袭伴随着 N-钙粘蛋白和纤连蛋白表达
DOI: 10.1016/j.bbrc.2007.05.023
发表时间: 2007-07-06
影响因子: 3.1
作者:
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