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Oncogene:同济大学薛雷与张帆课题组共同发现原癌基因Myc能抑制肿瘤迁移

摘要 : 2017年1月9日,国际学术权威刊物自然出版集团旗下子刊、肿瘤学重要学术期刊《Oncogene》杂志在线发表了同济大学生命科学院薛雷教授课题组和张帆教授课题组合作的研究论文.

2017年1月9日,国际学术权威刊物自然出版集团旗下子刊、肿瘤学重要学术期刊《Oncogene》杂志在线发表了同济大学生命科学院薛雷教授课题组和张帆教授课题组合作的题为“Myc suppresses tumor invasion and cell migration by inhibiting JNK signaling”研究论文。薛雷研究组的马仙珏、黄玖红及张帆研究组的田野为论文共同第一作者,薛雷课与张帆为论文通讯作者。

肿瘤迁移是癌症致死的主要原因,探明肿瘤迁移的分子机制是预防和治疗癌症的关键。Myc是一个重要的原癌基因,在大多数人类癌症中表达量升高,并与肿瘤的发生密切相关,但其在肿瘤细胞侵袭和迁移中的作用仍存在很大争议。薛雷教授课题组利用果蝇建立了肿瘤迁移的动物模型,并以此开展大规模的遗传筛选,发现Myc不仅能够抑制肿瘤浸润,还能调控正常发育中的细胞迁移。研究发现Myc和Max形成二聚体,作为转录因子结合在puc基因的调控区,激活puc的表达,从而抑制JNK信号通路介导的细胞迁移和肿瘤浸润。在果蝇中表达人类同源基因cMyc,也能有效的抑制细胞迁移和肿瘤浸润,证明Myc的这项功能在进化中高度保守。张帆教授课题组在体外培养的人类肺癌细胞PC9中进一步证实,过表达cMyc能下调JNK信号通路并减缓肺癌细胞的迁移;反之,敲低cMyc则上调JNK信号通路并促进肿瘤细胞的迁移。该研究不仅揭示了Myc对细胞迁移和肿瘤浸润的调控机制,也为Myc相关癌症的治疗提供了理论依据。

原文链接:

Myc suppresses tumor invasion and cell migration by inhibiting JNK signaling

原文摘要:

Tumor metastasis, but not primary overgrowth, is the leading cause of mortality for cancer patients. During the past decade, Drosophila melanogaster has been well-accepted as an excellent model to address the intrinsic mechanism of different aspects of cancer progression, ranging from tumor initiation to metastasis. In a genetic screen performed in Drosophila, aiming to find novel modulators of tumor invasion, we identified the oncoprotein Myc as a negative regulator. While expression of Myc dramatically blocks tumor invasion and cell migration, loss of Myc promotes cell migration in vivo. The activity of Myc is further enhanced by the co-expression of its transcription partner Max. Mechanistically, we found Myc/Max directly upregulates the transcription of puc, which encodes an inhibitor of JNK signaling crucial for tumor invasion and cell migration. Furthermore, we demonstrated that human cMyc potently suppresses JNK-dependent cell invasion and migration in both Drosophila and lung adenocarcinoma cell lines. These findings provide novel molecular insights into Myc-mediated cancer progression and raise the noteworthy problem in therapeutic strategies as inhibiting Myc might conversely accelerate tumor metastasis.

来源: Oncogene 浏览次数:0

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