Melanoma revives an embryonic migration program to promote plasticity and invasion
Melanoma revives an embryonic migration program to promote plasticity and invasion
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DOI：
10.1111/j.1755-148x.2012.01025.x
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发表时间：
2012-09-01
影响因子：
4.3
通讯作者：
Kulesa, Paul M.
中科院分区：
文献类型：
--
作者：
Bailey, Caleb M.;Morrison, Jason A.;Kulesa, Paul M.
癌细胞必须调节可塑性和侵袭性才能存活和转移。然而，对抑制转移的靶向机制的识别一直很缓慢。在正常发育过程中驱动干细胞和祖细胞的信号程序为发现转移的共同机制提供了一条途径。利用鸡胚胎移植模型，我们比较了黑色素瘤和它们的胚胎前体神经脊的分子信号程序。我们报告恶性黑色素瘤细胞劫持了部分胚胎神经脊侵袭程序。与神经脊诱导、分层和迁移相关的基因由暴露在胚胎神经脊微环境中的黑色素瘤细胞动态调节。具体地说，我们证明了转移性黑色素瘤细胞利用神经脊相关受体酪氨酸激酶来增加可塑性和促进侵袭，而原代黑素细胞可能在相同的微环境条件下主动抑制这些反应。我们的结论是，神经脊发育基因的异常调节促进了恶性黑色素瘤的可塑性和侵袭性。
Cancer cells must regulate plasticity and invasion to survive and metastasize. However, the identification of targetable mechanisms to inhibit metastasis has been slow. Signaling programs that drive stem and progenitor cells during normal development offer an inroad to discover mechanisms common to metastasis. Using a chick embryo transplant model, we have compared molecular signaling programs of melanoma and their embryonic progenitors, the neural crest. We report that malignant melanoma cells hijack portions of the embryonic neural crest invasion program. Genes associated with neural crest induction, delamination, and migration are dynamically regulated by melanoma cells exposed to an embryonic neural crest microenvironment. Specifically, we demonstrate that metastatic melanoma cells exploit neural crest-related receptor tyrosine kinases to increase plasticity and facilitate invasion while primary melanocytes may actively suppress these responses under the same microenvironmental conditions. We conclude that aberrant regulation of neural crest developmental genes promotes plasticity and invasiveness in malignant melanoma.