Aberrant methylation and loss of CADM2 tumor suppressor expression is associated with human renal cell carcinoma tumor progression
Aberrant methylation and loss of CADM2 tumor suppressor expression is associated with human renal cell carcinoma tumor progression
复制标题
DOI：
10.1016/j.bbrc.2013.04.074
复制
发表时间：
2013-06-14
影响因子：
3.1
通讯作者：
Chang, Guimin
中科院分区：
文献类型：
--
作者：
He, Wei;Li, Xuesong;Chang, Guimin
细胞粘附分子（CADM）是一类功能包括维持细胞极性和抑制肿瘤的蛋白质家族。在这份报告中，我们表明，CADM 2基因在人类肾透明细胞癌中受到抑制的DNA启动子超甲基化和/或杂合性丢失。此外，CADM 2表达的缺失与较高的肿瘤病理学分期相关（p < 0.05）。CADM 2在肾癌细胞系786-O中的重新表达通过G1期细胞周期停滞和诱导凋亡在体外和小鼠异种移植物中显著抑制肿瘤细胞生长。慢病毒介导的CADM 2表达也显著抑制癌细胞的锚定非依赖性生长和侵袭。此外，使用siRNA抑制内源性CADM 2表达在极化的非致瘤性MDCK细胞中诱导致瘤性表型。因此，我们的结论是，CADM 2功能作为一种新的肿瘤抑制因子，并可能作为一个潜在的治疗靶点，人类肾细胞癌。(c)2013 Elsevier Inc. All rights reserved.
Cell adhesion molecules (CADMs) comprise a protein family whose functions include maintenance of cell polarity and tumor suppression. In this report, we show that the CADM2 gene is repressed in human clear renal cell carcinoma by DNA promoter hypermethylation and/or loss of heterozygosity. Moreover, the loss of CADM2 expression is associated with a higher tumor pathology stage (p < 0.05). The re-expression of CADM2 in the renal cancer cell line 786-O significantly suppressed tumor cell growth in vitro and in mouse xenografts by a G1 phase cell cycle arrest and the induction of apoptosis. Lentivirus-mediated CADM2 expression also significantly suppressed cancer cell anchorage-independent growth and invasion. Furthermore, the inhibition of endogenous CADM2 expression using siRNAs induced a tumorigenic phenotype in polarized non-tumorigenic MDCK cells. Thus, we conclude that CADM2 functions as a novel tumor suppressor and may serve as a potential therapeutic target for human renal cell carcinoma. (c) 2013 Elsevier Inc. All rights reserved.