Department of Colorectal Surgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China,
Target Oncol. 2014 Mar;9(1):53-61. doi: 10.1007/s11523-013-0269-6. Epub 2013 Feb 20.
δ-Catenin is the only member of the p120 catenin (p120ctn) subfamily whose normal pattern of expression is restricted to the brain. Similar to p120ctn, δ-catenin can bind to the juxtamembrane domain of E-cadherin. We examined the expression of δ-catenin, p120ctn, and E-cadherin using immunohistochemistry in 95 cases of colorectal cancer (CRC) and 15 normal colon tissues. Co-immunoprecipitation was used to examine whether δ-catenin competed with p120ctn to bind E-cadherin in CRC cells. The effects of δ-catenin overexpression or siRNA-mediated knockdown on the proliferation and invasive ability of CRC cells were investigated using the MTT and Matrigel invasion assays. The results showed that positive δ-catenin expression was significantly more frequent in CRC compared to normal colon tissues and associated with poor differentiation, stage III-IV disease, and lymph node metastasis in CRC (all P < 0.05). In two CRC cell lines, δ-catenin bound to E-cadherin in competition with p120ctn. Overexpression of δ-catenin promoted the proliferation and invasion of CRC cells; knockdown of δ-catenin reduced CRC cell proliferation and invasion. In conclusion, we speculate that overexpression of δ-catenin reduces the expression of E-cadherin and alters the balance between E-cadherin and p120ctn, which in turn affects the formation of intercellular adhesions and promotes invasion and metastasis in CRC.
δ-连环蛋白是 p120 连环蛋白 (p120ctn) 亚家族中唯一正常表达局限于大脑的成员。与 p120ctn 相似，δ-连环蛋白可以与 E-钙黏蛋白的跨膜区结合。我们使用免疫组织化学方法检测了 95 例结直肠癌 (CRC) 和 15 例正常结肠组织中 δ-连环蛋白、p120ctn 和 E-钙黏蛋白的表达。我们使用共免疫沉淀来检测在 CRC 细胞中 δ-连环蛋白是否与 p120ctn 竞争结合 E-钙黏蛋白。我们通过 MTT 和 Matrigel 侵袭实验研究了 δ-连环蛋白过表达或 siRNA 介导的敲低对 CRC 细胞增殖和侵袭能力的影响。结果表明，与正常结肠组织相比，CRC 中 δ-连环蛋白的阳性表达更为频繁，并且与 CRC 中分化不良、III-IV 期疾病和淋巴结转移有关（均 P<0.05）。在两种 CRC 细胞系中，δ-连环蛋白与 p120ctn 竞争结合 E-钙黏蛋白。δ-连环蛋白的过表达促进了 CRC 细胞的增殖和侵袭；δ-连环蛋白的敲低减少了 CRC 细胞的增殖和侵袭。总之，我们推测 δ-连环蛋白的过表达降低了 E-钙黏蛋白的表达，并改变了 E-钙黏蛋白与 p120ctn 之间的平衡，从而影响了细胞间黏附的形成，并促进了 CRC 的侵袭和转移。
