Farooqi Ammad Ahmad, Li Yiwei, Sarkar Fazlul H
Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College, Lahore, Pakistan.
Departments of Pathology and Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA.
Exp Mol Med. 2015 Sep 25;47(9):e185. doi: 10.1038/emm.2015.70.
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.
Raf激酶抑制蛋白（RKIP）已被证明可调节癌症中的不同细胞内信号通路。研究表明，RKIP在癌症中经常下调；因此，人们尝试使用天然和合成药物上调RKIP的表达以治疗人类恶性肿瘤。此外，还发现了各种参与RKIP表达调控的调节因子，如特定蛋白质和微小RNA（miRNA）。RKIP在机制上调节肿瘤坏死因子相关凋亡诱导配体（TRAIL）信号通路的凋亡调节因子。由于其在人类癌症中的关键作用，RKIP引起了很多研究关注，我们对它的了解也在迅速扩展。在此，我们总结RKIP调控的一些生物学复杂性。然而，我们通过聚焦TRAIL、miRNA和天然药物，将讨论限制在特定肿瘤上。新出现的证据表明天然药物在癌细胞RKIP调控中发挥作用；因此，天然存在的药物可能作为癌症治疗的靶向药物。尽管文献表明我们对RKIP生物学的认识有了一些进展，但其临床前和临床疗效方面仍不完整；因此，有必要进一步研究。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如何用于治疗仍有待确定。
