Odintsova E, Sugiura T, Berditchevski F
CRC Institute for Cancer Studies, The University of Birmingham, Edgbaston, UK.
Curr Biol. 2000 Aug 24;10(16):1009-12. doi: 10.1016/s0960-9822(00)00652-7.
The 'metastasis suppressor' CD82/KAI-1, a member of the tetraspanin superfamily of transmembrane proteins, is widely distributed in normal tissues [1], and has been shown to be suppressed in the advanced stages of various epithelial malignancies [2-6]. Although the physiological relevance of this change is unknown, in vitro data show that ectopically expressed CD82/KAI-1 can suppress tumor cell migration, a process underlying the dissemination of tumor cells in vivo [5]. The function of CD82/KAI-1 is not known and it has been proposed that association of CD82/KAI-1 with other cell-surface proteins may be pivotal in directing its biological activities [7,8]. We show here that the CD82/KAI-1 tetraspanin is directly associated with the EGF receptor (EGFR), and that ectopic expression of CD82/KAI-1 in epithelial cells specifically suppresses EGF-induced lamellipodial extensions and cell migration. In cells expressing CD82/KAI-1, the initial activation of EGFR is not affected, but subsequent desensitization of EGF-induced signaling occurs more rapidly. This attenuation is correlated with an increased rate of receptor endocytosis. These results identify CD82/KAI-1 as a new regulator of EGF-induced signaling and show that the association of EGFR with the tetraspanin is critical in EGFR desensitization.
“转移抑制因子”CD82/KAI-1是跨膜蛋白四跨膜超家族的成员之一，广泛分布于正常组织中[1]，并且已证实在多种上皮恶性肿瘤的晚期阶段其表达受到抑制[2-6]。尽管这种变化的生理相关性尚不清楚，但体外实验数据表明，异位表达的CD82/KAI-1能够抑制肿瘤细胞迁移，而肿瘤细胞迁移是肿瘤细胞在体内扩散的一个过程[5]。CD82/KAI-1的功能尚不清楚，有人提出CD82/KAI-1与其他细胞表面蛋白的结合可能对其生物学活性起关键作用[7,8]。我们在此表明，CD82/KAI-1四跨膜蛋白与表皮生长因子受体（EGFR）直接相关，并且上皮细胞中CD82/KAI-1的异位表达特异性地抑制了表皮生长因子诱导的片状伪足延伸和细胞迁移。在表达CD82/KAI-1的细胞中，表皮生长因子受体的初始激活不受影响，但随后表皮生长因子诱导的信号脱敏发生得更快。这种减弱与受体胞吞作用速率的增加相关。这些结果确定CD82/KAI-1是表皮生长因子诱导信号的一种新调节因子，并表明表皮生长因子受体与四跨膜蛋白的结合在表皮生长因子受体脱敏中起关键作用。
