The biological complexity of RKIP signaling in human cancers.
The biological complexity of RKIP signaling in human cancers.
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DOI：
10.1038/emm.2015.70
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发表时间：
2015-09-25
影响因子：
12.8
通讯作者：
Sarkar FH
中科院分区：
文献类型：
--
作者：
Farooqi AA;Li Y;Sarkar FH
Raf激酶抑制蛋白（RKIP）已被证明可以调节癌症中不同的细胞内信号传导途径。研究表明，RKIP在癌症中经常下调;因此，已经尝试使用天然和合成试剂上调RKIP的表达以治疗人类恶性肿瘤。此外，还鉴定了参与RKIP表达调节的各种调节剂，如特异性蛋白质和microRNA（miRNA）。RKIP机制性地调节肿瘤坏死因子相关凋亡诱导配体（TRAIL）信号传导的凋亡调节因子。由于其在人类癌症中的关键作用，RKIP引起了许多研究的关注，我们的理解正在迅速扩大。在这里，我们总结了一些RKIP调节的生物学复杂性。然而，我们的讨论仅限于选定的肿瘤，主要集中在TRAIL，miRNA和天然药物。新出现的证据表明，天然药物在癌细胞中的RKIP调节中发挥作用;因此，天然药物可作为癌症治疗的癌症靶向药物。尽管文献表明我们对RKIP生物学的了解有所进展，但其临床前和临床疗效仍不完整;因此，需要进一步研究。此外，化疗药物和新型化合物调节RKIP的机制以及纳米技术递送的RKIP如何在治疗上被利用仍有待确定。
The Raf kinase inhibitory protein (RKIP) has been demonstrated to modulate different intracellular signaling pathways in cancers. Studies have shown that RKIP is frequently downregulated in cancers; therefore, attempts have been made to upregulate the expression of RKIP using natural and synthetic agents for the treatment of human malignancies. Moreover, various regulators such as specific proteins and microRNAs (miRNAs) that are involved in the regulation of RKIP expression have also been identified. RKIP mechanistically modulates the apoptotic regulators of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling. Because of its critical role in human cancers, RKIP has drawn much research attention, and our understanding is expanding rapidly. Here, we summarize some of the biological complexities of RKIP regulation. However, we restrict our discussion to selected tumors by focusing on TRAIL, miRNAs and natural agents. Emerging evidence suggests a role for natural agents in RKIP regulation in cancer cells; therefore, naturally occurring agents may serve as cancer-targeting agents for cancer treatment. Although the literature suggests some advancement in our knowledge of RKIP biology, it is incomplete with regard to its preclinical and clinical efficacy; thus, further research is warranted. Furthermore, the mechanism by which chemotherapeutic drugs and novel compounds modulate RKIP and how nanotechnologically delivered RKIP can be therapeutically exploited remain to be determined.