JNK Signaling in the Control of the Tumor-Initiating Capacity Associated with Cancer Stem Cells.
JNK Signaling in the Control of the Tumor-Initiating Capacity Associated with Cancer Stem Cells.
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DOI：
10.1177/1947601912474892
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发表时间：
2013-09-01
期刊：
影响因子：
--
通讯作者：
Okada, Masashi
中科院分区：
文献类型：
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作者：
Kitanaka, Chifumi;Sato, Atsushi;Okada, Masashi
c-Jun NH 2-末端激酶（JNK）信号转导的失调经常发生在各种人类癌症中，但JNK失调在癌细胞生物学中的确切作用仍有待充分阐明。我们最近的研究表明，JNK的活性不仅是神经胶质瘤干细胞自我更新所必需的，而且也是其肿瘤起始所必需的，然而，已经确定了JNK在控制癌细胞的干细胞性和肿瘤起始能力中的新作用。值得注意的是，瞬时JNK抑制足以导致神经胶质瘤干细胞的肿瘤起始能力的持续丧失，这表明“丧失的肿瘤起始能力”的表型可能与分化状态一样稳定，因此肿瘤起始能力可能通过也支配干细胞性和分化的表观遗传机制在JNK的控制下。在这里，在这篇文章中，我们审查JNK的作用和机制，在控制这个“干细胞相关的肿瘤启动能力”（STATIC），一个新的假设概念，我们在这篇评论文章介绍。由于STATIC的概念基本上适用于遵循和不遵循癌症干细胞假说的两种癌症类型，因此我们还考虑了JNK介导的STATIC控制在JNK异常激活的广泛人类癌症中的可能参与。从理论上讲，通过JNK成功靶向STATIC可能有助于长期控制癌症。针对JNK-STATIC轴的治疗的临床应用之前要考虑的问题也进行了讨论。
Deregulation of c-Jun NH2-terminal kinase (JNK) signaling occurs frequently in a variety of human cancers, yet the exact role(s) of JNK deregulation in cancer cell biology remains to be fully elucidated. Our recent demonstration that the activity of JNK is required not only for self-renewal of glioma stem cells but also for their tumor initiation has, however, identified a new role for JNK in the control of the stemness and tumor-initiating capacity of cancer cells. Significantly, transient JNK inhibition was sufficient to cause sustained loss of the tumor-initiating capacity of glioma stem cells, suggesting that the phenotype of "lost tumor-initiating capacity" may be as stable as the differentiated state and that the tumor-initiating capacity might therefore be under the control of JNK through an epigenetic mechanism that also governs stemness and differentiation. Here, in this article, we review the role and mechanism of JNK in the control of this "stemness-associated tumor-initiating capacity" (STATIC), a new hypothetical concept we introduce in this review article. Since the idea of STATIC is essentially applicable to both cancer types that do and do not follow the cancer stem cell hypothesis, we also give consideration to the possible involvement of JNK-mediated control of STATIC in a wide range of human cancers in which JNK is aberrantly activated. Theoretically, successful targeting of STATIC through JNK could contribute to long-term control of cancer. Issues to be considered before clinical application of therapies targeting this JNK-STATIC axis are also discussed.