P-Rex1 is required for efficient melanoblast migration and melanoma metastasis.

P-Rex1 is required for efficient melanoblast migration and melanoma metastasis.
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P-Rex1 是有效的成黑细胞迁移和黑色素瘤转移所必需的。

DOI:
10.1038/ncomms1560
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发表时间:
2011-11-22
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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转移是黑色素瘤死亡的主要原因,黑色素瘤是一种皮肤癌,在西方世界的任何恶性肿瘤中发病率上升最快。在发育过程中驱动成黑素细胞迁移的分子途径被认为是黑色素瘤运动和最终转移的基础。在这里,我们表明,小鼠缺乏P-Rex 1,一种Rac特异性Rho GTdR鸟嘌呤核苷酸交换因子(GEF),在发育过程中有一个黑色素母细胞迁移缺陷证明了一个白色的腹部。此外,这些P-Rex 1 −/−小鼠在与黑色素瘤小鼠模型杂交时对转移具有抗性。从机制上讲,这与P-Rex 1以Rac依赖的方式驱动入侵有关。P-Rex 1在绝大多数人黑色素瘤细胞系以及肿瘤组织中升高。我们的结论是,P-Rex 1在小鼠和人类的黑色素母细胞迁移和癌症进展到转移中起着重要作用。
Metastases are the major cause of death from melanoma, a skin cancer which 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 (GEF), 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 great majority of human melanoma cell lines as well as tumor tissue. We conclude that P-Rex1 plays an important role in melanoblast migration and cancer progression to metastasis in mice and humans.
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