EphA2 is a critical oncogene in melanoma.
EphA2 is a critical oncogene in melanoma.
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DOI：
10.1038/onc.2011.210
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发表时间：
2011-12-15
期刊：
影响因子：
8
通讯作者：
Tsao, H.
中科院分区：
文献类型：
--
作者：
Udayakumar, D.;Zhang, G.;Ji, Z.;Njauw, C-N;Mroz, P.;Tsao, H.
EphA2是Eph受体酪氨酸激酶家族的成员，在包括黑色素瘤在内的许多侵袭性癌症类型中高度表达。我们最近发现EphA2也被紫外线辐射上调，并能够诱导细胞凋亡。这些发现表明，根据细胞环境的不同，EphA2对细胞活力的影响可能是不同的，甚至是自相矛盾的，EphA2在细胞的生死之间调节着微妙的平衡。为了从功能上阐明EphA2‘S在黑色素瘤中的作用，我们分析了一组黑色素瘤细胞系，发现EphA2水平在很大一部分样本中升高。使用shRNA特异性耗尽高表达黑色素瘤细胞中的EphA2会导致细胞存活率、体外克隆形成和迁移的显著降低，以及体内致瘤潜力的显著丧失。稳定地将EphA2导入低表达细胞系可促进其增殖、集落形成和迁移，进一步支持其恶性表型。有趣的是，在未转化的黑素细胞中瞬时表达EphA2和/或BRAFV600E会导致显著的可加性凋亡。这些结果证实了EphA2是一种重要的癌基因，也是许多黑色素瘤细胞共同的“瘾”来源。此外，EphA2的急性诱导可能会清除遗传敏感的细胞，从而揭示出实际上依赖于癌基因的更具侵略性的人群。
EphA2 is a member of the Eph family of receptor tyrosine kinases and is highly expressed in many aggressive cancer types, including melanoma. We recently showed that EphA2 is also upregulated by ultraviolet radiation and is able to induce apoptosis. These findings suggest that EphA2 may have different, even paradoxical, effects on viability depending on the cellular context and that EphA2 mediates a delicate balance between life and death of the cell. To functionally clarify EphA2’s role in melanoma, we analyzed a panel of melanoma cell lines and found that EphA2 levels are elevated in a significant fraction of the samples. Specific depletion of EphA2 in high-expressing melanoma cells using shRNA led to profound reductions in cellular viability, colony formation and migration in vitro and a dramatic loss of tumorigenic potential in vivo. Stable introduction of EphA2 into low-expressing lines enhanced proliferation, colony formation and migration further supporting its pro-malignant phenotype. Interestingly, transient expression of EphA2 and/or BrafV600E in non-transformed melanocytes led to significant and additive apoptosis. These results verify that EphA2 is an important oncogene and potentially a common source of “addiction” for many melanoma cells. Moreover, acute induction of EphA2 may purge genetically-susceptible cells thereby uncovering a more aggressive population that is in fact dependent on the oncogene.
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影响因子：
64.8
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影响因子：
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作者：
Kamat AA;Coffey D;Merritt WM;Nugent E;Urbauer D;Lin YG;Edwards C;Broaddus R;Coleman RL;Sood AK
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通讯作者：
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通讯作者：
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