摘要
恶意的黑瘤，由侵略本地生长和转移的早形成描绘了，是皮癌症的最好攻击的类型。黑瘤禁止的活动(MIA ) ，由恶意的黑瘤房间藏匿了，与房间粘附受体， integrins 伪 4 尾 1 和伪 5 尾 1，便于的房间分开和转移的支持的形成交往。在现在的学习，我们证明那 MIA 分泌物被限制到移植房间的后面的目的，当在非移居的房间 MIA 在肌动朊外皮积累时。MIA 蛋白质包括上衣蛋白质建筑群拿一条常规能分泌的小径我(COPI )- 并且上衣蛋白质建筑群 II (COPII ) 依赖者蛋白质运输到房间圆周，在它的最后的版本取决于细胞内部的 Ca2+ 离子的地方。有趣地，激活 Ca2+ 的 K+ 隧道，亚科 N，成员 4 (KCa3.1 ) ，知道在移植房间的后面的结束活跃，被发现支持 MIA 分泌物。分泌物被特定的 KCa3.1 隧道禁止者 TRAM-34 并且由隧道的主导否定的异种的表示减少。在摘要，我们阐明了到房间尾部并且也的 MIA 蛋白质的联系迁居的运输揭示了 KCa3.1 钾隧道由支持房间移植的新机制。
Malignant melanoma, characterized by invasive local growth and early formation of metastases, is the most aggressive type of skin cancer. Melanoma inhibitory activity （MIA）, secreted by malignant melanoma cells, interacts with the cell adhesion receptors, integrins a4131 and 05131, facilitating cell detachment and promoting formation of me- tastases. In the present study, we demonstrate that MIA secretion is confined to the rear end of migrating cells, while in non-migrating cells MIA accumulates in the actin cortex. MIA protein takes a conventional secretory pathway including coat protein complex I （COPI）- and coat protein complex II （COPII）-dependent protein transport to the cell periphery, where its final release depends on intracellular Ca2＋ ions. Interestingly, the Ca2＋-activated K＋-channel, subfamily N, member 4 （KCa3.1）, known to be active at the rear end of migrating cells, was found to support MIA secretion. Secretion was diminished by the specific KCa3.1 channel inhibitor TRAM-34 and by expression of dominant- negative mutants of the channel. In summary, we have elucidated the migration-associated transport of MIA protein to the cell rear and also disclosed a new mechanism by which KCa3.1 potassium channels promote cell migration.
