Control of cell motility by interaction of gangliosides, tetraspanins, and epidermal growth factor receptor in A431 versus KB epidermoid tumor cells
Control of cell motility by interaction of gangliosides, tetraspanins, and epidermal growth factor receptor in A431 versus KB epidermoid tumor cells
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DOI：
10.1016/j.carres.2009.04.032
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发表时间：
2009-08-17
影响因子：
3.1
通讯作者：
Hakomori, Sen-itiroh
中科院分区：
文献类型：
--
作者：
Park, Seung-Yeol;Yoon, Seon-Joo;Hakomori, Sen-itiroh
表皮样癌细胞系A431和KB的生长是由表皮生长因子（EGF）及其受体（EGFR）与酪氨酸激酶相互作用控制的。神经节苷脂GM 3以前被发现与EGFR相互作用并抑制EGFR酪氨酸激酶。然而，这些细胞的运动，控制EGFR和神经节苷脂，没有研究。本研究的重点是通过神经节苷脂，四跨膜蛋白（TSP）和EGFR的相互作用，这些细胞的运动的控制机制。主要成果如下：（i）A431细胞中表达的EGFR水平比KB细胞中表达的EGFR水平高约6倍，A431细胞的运动性也比KB细胞高得多，但A431细胞的生长不受EGF影响或被EGF抑制。相反，KB细胞的生长被EGF增强。(ii)在A431细胞中表达的TSP（CD 9、CD 82和CD 81）的水平比在KB细胞中表达的水平高得多，并且通过用EtDO-P4处理细胞来降低在A431细胞中表达的TSP，EtDO-P4抑制鞘糖脂（GSL）和神经节苷脂的合成。(iii)在A431和KB细胞中，这些TSP与EGFR共免疫沉淀，表明TSP与EGFR密切相关。(iv)通过用EtDO-P4处理细胞，A431细胞的高运动性大大降低，而KB细胞的低运动性不受影响。这些结果表明，A431细胞的高运动性与EGFR和TSP的高表达之间以及神经节苷脂GM 3/GM 2和TSP之间存在密切的相关性。KB细胞的低运动性与EGFR和TSP的低水平之间存在类似的相关性。A431细胞中高运动性和高水平EGFR与神经节苷脂-TSP复合物之间的相关性是独特的。这与我们以前的研究相反，我们以前的研究表明，许多类型的肿瘤细胞的运动性受到高水平的CD 9或CD 82以及生长因子受体和整合素的抑制。(C)2009年由Elsevier Ltd.出版
Growth of epidermoid carcinoma cell lines, A431 and KB, has been known to be controlled by the interaction of epidermal growth factor (EGF) and its receptor (EGFR) with tyrosine kinase. Ganglioside GM3 was previously found to interact with EGFR and to inhibit EGFR tyrosine kinase. However, motility of these cells, controlled by EGFR and ganglioside, was not studied. The present study is focused on the control mechanism of the motility of these cells through interaction of ganglioside, tetraspanin (TSP), and EGFR. Key results are as follows: (i) The level of EGFR expressed in A431 cells is similar to 6 times higher than that expressed in KB cells, and motility of A431 cells is also much higher than that of KB cells, yet growth of A431 cells is either not affected or is inhibited by EGF. In contrast, growth of KB cells is enhanced by EGF. (ii) Levels of TSPs (CD9, CD82, and CD81) expressed in A431 cells are Much higher than those expressed in KB cells, and TSPs expressed in A431 cells are reduced by treatment of cells with EtDO-P4, which inhibits the synthesis of glycosphingolipids (GSLs) and gangliosides. (iii) These TSPs are co-immunoprecipitated with EGFR in both A431 and KB cells, indicating that TSPs are closely associated with EGFR. (iv) High motility of A431 cells is greatly reduced, while low motility of KB cells is not affected, by treatment of cells with EtDO-P4. These results, taken together, suggest that there is a close correlation between high motility of A431 cells and high expression of EGFR and TSPs, and between ganglioside GM3/GM2 and TSP. A similar correlation was suggested between the low motility of KB cells and low levels of EGFR and TSP. The correlation between high motility and high level of EGFR with the ganglioside-TSP complex in A431 cells is unique. This is in contrast to our previous studies that indicate that motility of many types of tumor cells is inhibited by a high level of CD9 or CD82, together with growth factor receptors and integrins. (C) 2009 Published by Elsevier Ltd.