ROCK inhibitor enhances the growth and migration of BRAF-mutant skin melanoma cells.
ROCK inhibitor enhances the growth and migration of BRAF-mutant skin melanoma cells.
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ROCK 抑制剂可增强 BRAF 突变皮肤黑色素瘤细胞的生长和迁移。
DOI：
10.1111/cas.13786
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发表时间：
2018-11
期刊：
影响因子：
5.7
通讯作者：
Wu X
中科院分区：
文献类型：
--
作者：
Chang F;Zhang Y;Mi J;Zhou Q;Bai F;Xu X;Fisher DE;Sun Q;Wu X
Rho相关蛋白激酶(ROCK)在不同类型细胞的增殖和迁移中起着至关重要的作用。ROCK抑制剂Y-27632曾被报道能抑制黑色素瘤细胞的生长，ROCK信号转导被认为是治疗黑色素瘤的靶点。然而，Y-27632对黑色素瘤细胞的负面作用主要见于对小鼠B16黑色素瘤细胞的研究。在这里，我们报道了ROCK抑制剂实际上在体外促进了人黑色素瘤细胞的生长和迁移。Y-27632可促进BRAF突变黑色素瘤细胞的生长和迁移，但对野生型黑色素瘤细胞和原代黑素细胞无明显影响。我们发现，Y-27632通过提高细胞信号转运蛋白和细胞外信号调节蛋白的活性，促进了突变黑色素瘤细胞的生长。体内研究进一步证实了体外研究结果。这些数据表明，ROCK抑制剂对黑色素瘤细胞的作用是细胞上下文依赖性的，ROCK抑制剂在黑色素瘤治疗中的应用有待进一步研究。
Rho‐associated protein kinase (ROCK) plays crucial roles in the proliferation and migration of different types of cells. ROCK inhibitor Y‐27632 was previously reported to inhibit melanoma cell growth, and ROCK signaling was suggested to be a therapeutic target for treating melanoma. However, the negative effect of Y‐27632 on melanoma cells was mainly seen in studies on murine B16 melanoma cells. Here, we reported that ROCK inhibitor actually promoted human melanoma cell growth and migration in vitro. Y‐27632 increased the growth and migration of BRAF‐mutated melanoma cells but had a negative effect on wild‐type melanoma cells or primary melanocytes. We discovered that Y‐27632 enhanced the growth of BRAF‐mutated melanoma cells through increased ATK and ERK activity. The in vivo study further confirmed the in vitro finding. These data suggested that the effect of ROCK inhibitor on melanoma cells is cell‐context dependent, and the application of ROCK inhibitor in the treatment of melanoma requires further study.
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DOI：
10.1007/978-1-4614-8244-4_10
发表时间：
2014-01-01
期刊：
METASTASIS RESEARCH PROTOCOLS, 2ND EDITION
影响因子：
--
作者：
Giavazzi, Raffaella;Decio, Alessandra
通讯作者：
Decio, Alessandra
影响因子：
5.2
作者：
Nakashima, Masanori;Adachi, Seiji;Moriwaki, Hisataka
通讯作者：
Moriwaki, Hisataka
影响因子：
56.9
作者：
Rommel, C;Clarke, BA;Glass, DJ
通讯作者：
Glass, DJ
影响因子：
7.3
作者：
Feng, Yangbo;LoGrasso, Philip V.;Li, Rongshi
通讯作者：
Li, Rongshi
影响因子：
3.2
作者：
Wei L;Surma M;Shi S;Lambert-Cheatham N;Shi J
通讯作者：
Shi J