Department of Molecular Cell Biology and Toxicology, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
Oncogene. 2010 Feb 25;29(8):1227-37. doi: 10.1038/onc.2009.408. Epub 2009 Nov 30.
JWA, a newly identified novel microtubule-associated protein (MAP), was recently demonstrated to be indispensable for the rearrangement of actin cytoskeleton and activation of MAPK cascades induced by arsenic trioxide (As(2)O(3)) and phorbol ester (PMA). JWA depletion blocked the inhibitory effect of As(2)O(3) on HeLa cell migration, but enhanced cell migration after PMA treatment. As cancer cell migration is a hallmark of tumor metastasis and the functional role of JWA in cancer metastasis is not understood, here we show that JWA has an important role in melanoma metastasis. Our data demonstrated that JWA knockdown increased the adhesion and invasion abilities of melanoma cells. Furthermore, JWA knockdown in B16-F10 and A375 melanoma cells significantly promoted the formation and growth of metastatic colonies in vivo. Moreover, in the tumor biopsies from human melanoma patients, JWA expression was significantly decreased in malignant melanoma compared with normal nevi. In addition, we found that JWA knockdown could intensify tumor integrin alpha(V)beta(3) signaling by regulating nuclear factor Sp1. These findings suggest that JWA suppresses melanoma metastasis and may serve a potential therapeutic target for human melanoma.
JWA 是一种新鉴定的微管相关蛋白 (MAP)，最近的研究表明它对于砷三氧化物 (As(2)O(3)) 和佛波酯 (PMA) 诱导的肌动蛋白细胞骨架重排和 MAPK 级联的激活是不可或缺的。JWA 耗尽阻断了 As(2)O(3)对 HeLa 细胞迁移的抑制作用，但增强了 PMA 处理后的细胞迁移。由于癌细胞迁移是肿瘤转移的一个标志，而 JWA 在癌症转移中的功能作用尚不清楚，因此我们在这里表明 JWA 在黑色素瘤转移中具有重要作用。我们的数据表明，JWA 敲低增加了黑色素瘤细胞的黏附和侵袭能力。此外，B16-F10 和 A375 黑色素瘤细胞中的 JWA 敲低显着促进了体内转移性集落的形成和生长。此外，在人类黑色素瘤患者的肿瘤活检中，与正常痣相比，恶性黑色素瘤中 JWA 的表达明显降低。此外，我们发现 JWA 敲低可以通过调节核因子 Sp1 来增强肿瘤整合素 alpha(V)beta(3)信号。这些发现表明 JWA 抑制黑色素瘤转移，可能成为人类黑色素瘤的潜在治疗靶点。
