The neural guidance receptor Plexin C1 delays melanoma progression.
The neural guidance receptor Plexin C1 delays melanoma progression.
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DOI：
10.1038/onc.2012.511
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发表时间：
2013-10-10
期刊：
影响因子：
8
通讯作者：
Scott, G.
中科院分区：
文献类型：
--
作者：
Chen, Y.;Soong, J.;Mohanty, S.;Xu, L.;Scott, G.
丛状蛋白C1是一种I型跨膜受体，具有内在的R-Ras GT3活性，调节正常人黑素细胞的细胞骨架重塑和粘附。黑素细胞是表皮的色素产生细胞，黑色素瘤的前体，并表达高水平的丛蛋白C1，其在体外和体内的黑色素瘤中丢失。为了确定丛蛋白C1是否是黑色素瘤的肿瘤抑制因子，我们将丛蛋白C1引入原代人黑色素瘤细胞系，并分析小鼠中的表型，包括迁移、凋亡、增殖和肿瘤生长。进行了丛状蛋白C1在人黑素细胞中沉默的补充研究。丛蛋白C1显着抑制黑色素瘤的迁移和增殖，而在黑素细胞，丛蛋白C1的损失增加迁移和增殖。在小鼠异种移植物中，丛蛋白C1在早期时间点延迟黑色素瘤的肿瘤生长，但由于丛蛋白C1依赖性激活促生存蛋白Akt，肿瘤最终逃脱了丛蛋白C1的抑制作用。R-Ras激活刺激黑色素瘤迁移。丛蛋白C1降低黑色素瘤和黑色素细胞中的R-Ras活性，这与丛蛋白C1对黑色素细胞和黑色素瘤迁移的抑制作用一致。为了确定R-Ras是否在体内黑素细胞病变中表达，对痣和黑色素瘤的组织微阵列进行染色。R-Ras表达在黑素细胞病变中高度受限，基本上局限于原发性黑色素瘤，并且在痣和转移性黑色素瘤中几乎完全不存在。这些数据表明，黑色素瘤中丛蛋白C1的缺失可能通过抑制迁移和增殖促进黑色素瘤进展的早期步骤，但丛蛋白C1的促存活作用最终消除了丛蛋白C1的肿瘤抑制作用。在原发性黑色素瘤中，丛状蛋白C1的缺失可能通过释放对R-Ras活化的抑制和刺激迁移在黑色素瘤进展的早期步骤中起作用。
Plexin C1 is a type I transmembrane receptor with intrinsic R-Ras GTPase activity, which regulates cytoskeletal remodeling and adhesion in normal human melanocytes. Melanocytes are pigment-producing cells of the epidermis, precursors for melanoma, and express high levels of Plexin C1, which is lost in melanoma in vitro and in vivo. To determine if Plexin C1 is a tumor suppressor for melanoma, we introduced Plexin C1 into a primary human melanoma cell line, and phenotypes including migration, apoptosis, proliferation and tumor growth in mice were analyzed. Complimentary studies in which Plexin C1 was silenced in human melanocytes were performed. Plexin C1 significantly inhibited migration and proliferation in melanoma, whereas in melanocytes, loss of Plexin C1 increased migration and proliferation. In mouse xenografts, Plexin C1 delayed tumor growth of melanoma at early time points, but tumors eventually escaped the suppressive effects of Plexin C1, due to Plexin C1-dependent activation of the pro-survival protein Akt. R-Ras activation stimulates melanoma migration. Plexin C1 lowered R-Ras activity in melanoma and melanocytes, consistent with inhibitory effects of Plexin C1 on migration of melanocytes and melanoma. To determine if R-Ras is expressed in melanocytic lesions in vivo, staining of tissue microarrays of nevi and melanoma were performed. R-Ras expression was highly limited in melanocytic lesions, being essentially confined to primary melanoma, and almost completely absent in nevi and metastatic melanoma. These data suggest that loss of Plexin C1 in melanoma may promote early steps in melanoma progression through suppression of migration and proliferation, but pro-survival effects of Plexin C1 ultimately abrogate the tumor suppressive effects of Plexin C1. In primary melanoma, loss of Plexin C1 may function in early steps of melanoma progression by releasing inhibition of R-Ras activation, and stimulating migration.
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影响因子：
3.7
作者：
Gawecka JE;Griffiths GS;Ek-Rylander B;Ramos JW;Matter ML
通讯作者：
Matter ML
DOI：
10.1083/jcb.145.5.1077
发表时间：
1999-05-31
期刊：
The Journal of cell biology
影响因子：
--
作者：
Keely PJ;Rusyn EV;Cox AD;Parise LV
通讯作者：
Parise LV
影响因子：
3.3
作者：
Iwasawa N;Negishi M;Oinuma I
通讯作者：
Oinuma I
影响因子：
4.8
作者：
Iwashita, Shintaro;Kobayashi, Mariko;Song, Si-Young
通讯作者：
Song, Si-Young
影响因子：
7.8
作者：
Oinuma, Izumi;Katoh, Hironori;Negishi, Manabu
通讯作者：
Negishi, Manabu