当前位置: X-MOL 学术Drug Resist. Updat. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Inverse correlation between the metastasis suppressor RKIP and the metastasis inducer YY1: Contrasting roles in the regulation of chemo/immuno-resistance in cancer
Drug Resistance Updates ( IF 24.3 ) Pub Date : 2017-01-09 , DOI: 10.1016/j.drup.2017.01.001
Stephanie Wottrich , Samantha Kaufhold , Emmanuel Chrysos , Odysseas Zoras , Stavroula Baritaki , Benjamin Bonavida

Several gene products have been postulated to mediate inherent and/or acquired anticancer drug resistance and tumor metastasis. Among these, the metastasis suppressor and chemo-immuno-sensitizing gene product, Raf Kinase Inhibitor Protein (RKIP), is poorly expressed in many cancers. In contrast, the metastasis inducer and chemo-immuno-resistant factor Yin Yang 1 (YY1) is overexpressed in many cancers. This inverse relationship between RKIP and YY1 expression suggests that these two gene products may be regulated via cross-talks of molecular signaling pathways, culminating in the expression of different phenotypes based on their targets. Analyses of the molecular regulation of the expression patterns of RKIP and YY1 as well as epigenetic, post-transcriptional, and post-translational regulation revealed the existence of several effector mechanisms and crosstalk pathways, of which five pathways of relevance have been identified and analyzed. The five examined cross-talk pathways include the following loops: RKIP/NF-κB/Snail/YY1, p38/MAPK/RKIP/GSK3β/Snail/YY1, RKIP/Smurf2/YY1/Snail, RKIP/MAPK/Myc/Let-7/HMGA2/Snail/YY1, as well as RKIP/GPCR/STAT3/miR-34/YY1. Each loop is comprised of multiple interactions and cascades that provide evidence for YY1’s negative regulation of RKIP expression and vice versa. These loops elucidate potential prognostic motifs and targets for therapeutic intervention. Chiefly, these findings suggest that targeted inhibition of YY1 by specific small molecule inhibitors and/or the specific induction of RKIP expression and activity are potential therapeutic strategies to block tumor growth and metastasis in many cancers, as well as to overcome anticancer drug resistance. These strategies present potential alternatives for their synergistic uses in combination with low doses of conventional chemo-immunotherapeutics and hence, increasing survival, reducing toxicity, and improving quality of life.



中文翻译:

转移抑制因子RKIP和转移诱导因子YY1之间的逆相关性:癌症化学/免疫抵抗调节中的不同作用

假定几种基因产物介导固有的和/或获得的抗癌药耐药性和肿瘤转移。其中,转移抑制和化学免疫致敏基因产物Raf激酶抑制剂蛋白(RKIP)在许多癌症中表达不佳。相反,在许多癌症中,转移诱导因子和化学免疫抗性因子Yin Yang 1(YY1)过表达。RKIP和YY1表达之间的这种逆向关系表明,这两个基因产物可能通过分子信号通路的串扰来调节,最终导致基于其靶标的不同表型的表达。分析RKIP和YY1表达模式的分子调控,以及表观遗传,转录后,翻译后调控揭示了几种效应器机制和串扰通路的存在,其中五个相关通路已被鉴定和分析。考察的五个串扰路径包括以下循环:RKIP /NF-κB/ Snail / YY1p38 / MAPK / RKIP /GSK3β/ Snail / YY1RKIP / Smurf2 / YY1 / SnailRKIP / MAPK / Myc / Let-7 / HMGA2 / Snail / YY1以及RKIP / GPCR / STAT3 / miR-34 / YY1。每个循环均由多个相互作用和级联组成,可为YY1对RKIP表达的负调控提供证据,反之亦然。这些循环阐明了潜在的预后基序和治疗干预目标。首先,这些发现表明,特定的小分子抑制剂对YY1的靶向抑制和/或RKIP表达和活性的特定诱导是阻止许多癌症中肿瘤生长和转移以及克服抗癌药物耐药性的潜在治疗策略。这些策略为与低剂量的常规化学免疫治疗剂协同使用提供了潜在的替代选择,从而提高了生存率,降低了毒性并改善了生活质量。

更新日期:2017-01-09
down
wechat
bug