P-Cadherin Promotes Liver Metastasis and Is Associated with Poor Prognosis in Colon Cancer
P-Cadherin Promotes Liver Metastasis and Is Associated with Poor Prognosis in Colon Cancer
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P-钙粘蛋白促进肝转移并与结肠癌的不良预后相关
DOI：
10.1016/j.ajpath.2011.03.046
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发表时间：
2011-07-01
影响因子：
6
通讯作者：
Ran, Yuliang
中科院分区：
文献类型：
--
作者：
Sun, Lichao;Hu, Hai;Ran, Yuliang
P-钙粘蛋白属于经典钙粘蛋白家族，其对于维持细胞定位和组织完整性是重要的。最近，它已成为明显的是，P-钙粘蛋白有助于许多肿瘤类型，包括黑色素瘤，前列腺癌，乳腺癌和结肠癌的肿瘤发生。虽然钙粘蛋白转换是转移的关键步骤，但P-钙粘蛋白在结肠癌向肝脏转移中的作用尚不清楚。在这项研究中，我们进行了基因表达分析，发现P-钙粘蛋白的水平是较高的组织从肝转移的结肠癌比相应的原发性结肠癌组织。免疫组化分析还显示，P-钙粘蛋白的表达显着高于肝转移瘤比配对的原发性结直肠癌肿瘤。敲低结肠癌细胞中的P-钙粘蛋白抑制伤口愈合、增殖和集落形成，并导致产生较少的肝转移灶和降低体内肿瘤负荷。抑制P-cadherin的表达也诱导E-cadherin的上调和β-catenin及其下游靶分子（包括survivin和c-Myc）的下调。总之，这些结果揭示了P-cadherin在调节结肠癌向肝转移中的新功能，表明阻断P-cadherin的活性或其相关信号传导可能是治疗结肠癌肝转移的有价值的靶点。(Am J Pathol 2011，179：380-390; DOI：10.1016/j.ajpath.2011.03.046）
P-cadherin belongs to the family of classic cadherins, which is important for maintaining cellular localization and tissue integrity. Recently, it has become evident that P-cadherin contributes to the oncogenesis of many tumor types, including melanoma, prostate, breast, and colon carcinomas. Although cadherin switching is a crucial step in metastasis, the role of P-cadherin in colon cancer metastasis to the liver is unknown. In this study, we performed gene expression analysis and found that the level of P-cadherin was higher in tissue from liver metastases of colon cancer than in the corresponding primary colon cancer tissues. IHC analysis also showed that P-cadherin expression was significantly higher in liver metastases than in paired primary colorectal cancer tumors. Knockdown of P-cadherin in colon cancer cells inhibited wound healing, proliferation, and colony formation and resulted in developing fewer liver metastatic foci and reducing the tumor burden in vivo. Inhibition of P-cadherin expression also induced the up-regulation of E-cadherin and the down-regulation of beta-catenin and its downstream target molecules, including survivin and c-Myc. In summary, these results uncover a novel function of P-cadherin in the regulation of colon cancer metastasis to the liver, suggesting that blocking the activity of P-cadherin or its associated signaling may be a valuable target for the treatment of hepatic metastases of colon carcinomas. (Am J Pathol 2011, 179:380-390; DOI: 10.1016/j.ajpath.2011.03.046)