The Beatson Institute for Cancer Research, Glasgow G61 1BD, UK.
Nat Commun. 2011 Nov 22;2:555. doi: 10.1038/ncomms1560.
Metastases are the major cause of death from melanoma, a skin cancer that has the fastest rising incidence of any malignancy in the Western world. Molecular pathways that drive melanoblast migration in development are believed to underpin the movement and ultimately the metastasis of melanoma. Here we show that mice lacking P-Rex1, a Rac-specific Rho GTPase guanine nucleotide exchange factor, have a melanoblast migration defect during development evidenced by a white belly. Moreover, these P-Rex1(-/-) mice are resistant to metastasis when crossed to a murine model of melanoma. Mechanistically, this is associated with P-Rex1 driving invasion in a Rac-dependent manner. P-Rex1 is elevated in the majority of human melanoma cell lines and tumour tissue. We conclude that P-Rex1 has an important role in melanoblast migration and cancer progression to metastasis in mice and humans.
转移是黑色素瘤（一种皮肤癌）患者死亡的主要原因，在西方世界，黑色素瘤的发病率上升速度最快。人们认为，在发育过程中驱动黑素细胞前体细胞迁移的分子途径是黑色素瘤迁移和最终转移的基础。在这里，我们发现缺乏 P-Rex1（一种 Rac 特异性 Rho GTPase 鸟嘌呤核苷酸交换因子）的小鼠在发育过程中存在黑素细胞前体细胞迁移缺陷的证据，表现为腹部变白。此外，当将这些 P-Rex1(-/-) 小鼠与黑色素瘤的小鼠模型杂交时，它们对转移具有抗性。从机制上讲，这与 P-Rex1 以 Rac 依赖性方式驱动侵袭有关。P-Rex1 在大多数人类黑色素瘤细胞系和肿瘤组织中升高。我们得出结论，P-Rex1 在小鼠和人类的黑素细胞前体细胞迁移和癌症进展转移中起重要作用。
