Evasion of anti-growth signaling: A key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds.
Evasion of anti-growth signaling: A key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds.
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DOI：
10.1016/j.semcancer.2015.02.005
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发表时间：
2015-12
影响因子：
14.5
通讯作者：
Shin DM
中科院分区：
文献类型：
--
作者：
Amin ARMR;Karpowicz PA;Carey TE;Arbiser J;Nahta R;Chen ZG;Dong JT;Kucuk O;Khan GN;Huang GS;Mi S;Lee HY;Reichrath J;Honoki K;Georgakilas AG;Amedei A;Amin A;Helferich B;Boosani CS;Ciriolo MR;Chen S;Mohammed SI;Azmi AS;Keith WN;Bhakta D;Halicka D;Niccolai E;Fujii H;Aquilano K;Ashraf SS;Nowsheen S;Yang X;Bilsland A;Shin DM
逃避抗生长信号传导是癌细胞的一个重要特征。为了继续增殖，癌细胞必须以某种方式使自己与减缓细胞生长的许多信号脱钩。在这里，我们定义了抗生长信号传导过程，并回顾了参与生长信号传导的几个重要途径：p53、磷酸酶和张力蛋白同源物（PTEN）、视网膜母细胞瘤蛋白（Rb）、Hippo、生长分化因子15（GDF15）、富含AT相互作用结构域1A（ARID1A）、Notch、胰岛素样生长因子（IGF）和Krüppel样因子5（KLF5）途径。癌细胞中这些过程的异常涉及突变，从而抑制阻止生长的基因，以及涉及驱动细胞生长的基因的突变和激活。以这些途径为例，我们优先考虑可用于促进癌细胞抗生长信号传导的分子靶点。有趣的是，人类饮食中天然存在的植物化学物质（无论是单独还是混合物）可能会促进抗生长信号传导，并且不会产生与合成化学物质相关的潜在不利影响。我们回顾了天然存在的植物化学物质的例子，这些植物化学物质可通过拮抗生长信号传导来预防癌症，并为每种途径提出一种植物化学物质。它们是：用于 Rb 途径的表没食子儿茶素-3-没食子酸酯 (EGCG)、用于 p53 的木犀草素、用于 PTEN 的姜黄素、用于 Hippo 的卟啉、用于 GDF15 的金雀异黄素、用于 ARID1A 的白藜芦醇、用于 Notch 的 withaferin A 和用于 IGF1 受体途径的地桂林。抗生长信号传导和天然化合物研究的协调将为这些化合物在临床环境中的未来应用提供见解。
The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting.