Department of Pathology, the First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.
Mol Carcinog. 2013 May;52(5):338-47. doi: 10.1002/mc.21854. Epub 2011 Dec 27.
δ-catenin can affect cytoskeletal assembly, and promote cell migration by regulating the activity of small GTPases. While many malignancies have been shown to be positive for δ-catenin, it is still unclear whether δ-catenin and small GTPases are coexpressed in tumor cells, and so is the relationship between their coexpression and prognosis in the tumor patients. In this study, immunohistochemistry was performed to examine expressive levels of δ-catenin, cdc42, and Rac1 in 135 cases of nonsmall cell lung cancer (NSCLC), including 60 cases with follow-up records. Thirty samples of paired lung cancer tissues and adjacent normal lung tissues were collected to analyze mRNA and protein expression of δ-catenin and small GTPases. The effects of δ-catenin on small GTPases expression and invasive ability of lung cancer cells were also evaluated. Compared with normal lung tissues, both mRNA and protein levels of δ-catenin and small GTPases were increased in lung cancer tissues (P < 0.05), and the expression of small GTPases directly correlated with that of δ-catenin (P < 0.001). In addition, δ-catenin and small GTPases tended to be coexpressed in lung adenocarcinoma, advanced stages, and primary tumors with lymph node metastasis (all P < 0.05). The patients with coexpression of δ-catenin and small GTPases had a shorter survival time than those without coexpression (P < 0.05). Furthermore, δ-catenin overexpression could enhance invasive ability of lung cancer cells by upregulating protein and transcriptional level of small GTPases. Therefore, δ-catenin likely upregulates the activity of small GTPases at transcriptional level, and their coexpression may predict a poor clinical outcome in NSCLC patients.
δ-连环蛋白可以通过调节小 GTP 酶的活性影响细胞骨架组装,并促进细胞迁移。虽然已经证实许多恶性肿瘤中 δ-连环蛋白呈阳性,但肿瘤细胞中 δ-连环蛋白和小 GTP 酶是否共表达,以及它们的共表达与肿瘤患者预后之间的关系尚不清楚。在这项研究中,通过免疫组织化学检测了 135 例非小细胞肺癌(NSCLC)患者肿瘤组织中 δ-连环蛋白、cdc42 和 Rac1 的表达水平,其中 60 例有随访记录。收集 30 对配对的肺癌组织和癌旁正常肺组织样本,分析 δ-连环蛋白和小 GTP 酶的 mRNA 和蛋白表达。还评估了 δ-连环蛋白对小 GTP 酶表达和肺癌细胞侵袭能力的影响。与正常肺组织相比,肺癌组织中 δ-连环蛋白和小 GTP 酶的 mRNA 和蛋白水平均升高(P<0.05),并且小 GTP 酶的表达与 δ-连环蛋白的表达直接相关(P<0.001)。此外,δ-连环蛋白和小 GTP 酶在肺腺癌、晚期和有淋巴结转移的原发性肿瘤中倾向于共表达(均 P<0.05)。共表达 δ-连环蛋白和小 GTP 酶的患者生存时间短于不共表达的患者(P<0.05)。此外,过表达 δ-连环蛋白可以通过上调小 GTP 酶的蛋白和转录水平来增强肺癌细胞的侵袭能力。因此,δ-连环蛋白可能在转录水平上调小 GTP 酶的活性,它们的共表达可能预示着 NSCLC 患者的临床预后不良。