Lallemand Dominique, Curto Marcello, Saotome Ichiko, Giovannini Marco, McClatchey Andrea I
MGH Cancer Center and Harvard Medical School Department of Pathology, Charlestown, Massachusetts 02129, USA.
Genes Dev. 2003 May 1;17(9):1090-100. doi: 10.1101/gad.1054603. Epub 2003 Apr 14.
Mutation of the Neurofibromatosis 2 (NF2) tumor suppressor gene leads to cancer development in humans and mice. Recent studies suggest that Nf2 loss also contributes to tumor metastasis. The Nf2-encoded protein, merlin, is related to the ERM (ezrin, radixin, and moesin) family of membrane:cytoskeleton-associated proteins. However, the cellular mechanism whereby merlin controls cell proliferation from this location is not known. Here we show that the major cellular consequence of Nf2 deficiency in primary cells is an inability to undergo contact-dependent growth arrest and to form stable cadherin-containing cell:cell junctions. Merlin colocalizes and interacts with adherens junction (AJ) components in confluent wild-type cells, suggesting that the lack of AJs and contact-dependent growth arrest in Nf2(-/-) cells directly results from the absence of merlin at sites of cell:cell contact. Our studies indicate that merlin functions as a tumor and metastasis suppressor by controlling cadherin-mediated cell:cell contact.
神经纤维瘤病2型（NF2）肿瘤抑制基因的突变会导致人类和小鼠发生癌症。最近的研究表明，Nf2缺失也会促进肿瘤转移。Nf2编码的蛋白merlin与膜：细胞骨架相关蛋白的ERM（埃兹蛋白、根蛋白和膜突蛋白）家族有关。然而，merlin从该位置控制细胞增殖的细胞机制尚不清楚。在这里，我们表明原代细胞中Nf2缺陷的主要细胞后果是无法经历接触依赖性生长停滞并形成稳定的含钙黏着蛋白的细胞间连接。Merlin在汇合的野生型细胞中与黏着连接（AJ）成分共定位并相互作用，这表明Nf2（-/-）细胞中缺乏AJ和接触依赖性生长停滞直接是由于细胞间接触部位缺乏merlin所致。我们的研究表明，merlin通过控制钙黏着蛋白介导的细胞间接触发挥肿瘤和转移抑制因子的作用。
