Microenvironmental Signals and Biochemical Information Processing: Cooperative Determinants of Intratumoral Plasticity and Heterogeneity.
Microenvironmental Signals and Biochemical Information Processing: Cooperative Determinants of Intratumoral Plasticity and Heterogeneity.
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DOI：
10.3389/fcell.2018.00044
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发表时间：
2018
影响因子：
5.5
通讯作者：
Albeck JG
中科院分区：
文献类型：
--
作者：
Davies AE;Albeck JG
肿瘤内细胞异质性是癌症治疗中的主要挑战。肿瘤由多个表型亚群组成，这些亚群在引发转移性肿瘤的能力和对化疗的敏感性方面各不相同。在许多情况下，细胞可以在这些亚群之间转换，不是通过基因突变，而是通过信号转导或基因表达程序的可逆变化。这种可塑性始于微环境的水平，其中局部自分泌和旁分泌信号、外泌体、肿瘤-基质相互作用和细胞外基质（ECM）组成创建随空间和时间变化的信号传导景观。这种复杂信号阵列的整合参与控制基因表达的信号传导途径。由此产生的基因表达程序的调节导致个体细胞对支持肿瘤生长、传播和治疗抗性的各种表型状态进行采样。在这篇综述中，我们讨论了信息如何在微环境景观动态流动，以告知细胞状态的决定，并创造肿瘤内的异质性。我们解决了可塑性在获得短暂和长期耐药状态中的作用，并讨论了如何有针对性的药理学修饰的信号转导景观可能能够约束表型可塑性，从而改善治疗反应。
Intra-tumor cellular heterogeneity is a major challenge in cancer therapy. Tumors are composed of multiple phenotypic subpopulations that vary in their ability to initiate metastatic tumors and in their sensitivity to chemotherapy. In many cases, cells can transition between these subpopulations, not by genetic mutation, but instead through reversible changes in signal transduction or gene expression programs. This plasticity begins at the level of the microenvironment where local autocrine and paracrine signals, exosomes, tumor–stroma interactions, and extracellular matrix (ECM) composition create a signaling landscape that varies over space and time. The integration of this complex array of signals engages signaling pathways that control gene expression. The resulting modulation of gene expression programs causes individual cells to sample a wide array of phenotypic states that support tumor growth, dissemination, and therapeutic resistance. In this review, we discuss how information flows dynamically within the microenvironmental landscape to inform cell state decisions and to create intra-tumoral heterogeneity. We address the role of plasticity in the acquisition of transient and prolonged drug resistant states and discuss how targeted pharmacological modification of the signaling landscape may be able to constrain phenotypic plasticity, leading to improved treatment responses.
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影响因子：
64.5
作者：
Boelens MC;Wu TJ;Nabet BY;Xu B;Qiu Y;Yoon T;Azzam DJ;Twyman-Saint Victor C;Wiemann BZ;Ishwaran H;Ter Brugge PJ;Jonkers J;Slingerland J;Minn AJ
通讯作者：
Minn AJ
影响因子：
50.3
作者：
Certo, Michael;Moore, Victoria Del Gaizo;Letai, Anthony
通讯作者：
Letai, Anthony
影响因子：
50.3
作者：
Becker A;Thakur BK;Weiss JM;Kim HS;Peinado H;Lyden D
通讯作者：
Lyden D
DOI：
10.1039/c5ib00040h
发表时间：
2015-10
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Acerbi I;Cassereau L;Dean I;Shi Q;Au A;Park C;Chen YY;Liphardt J;Hwang ES;Weaver VM
通讯作者：
Weaver VM
影响因子：
10.6
作者：
Abdullah LN;Chow EK
通讯作者：
Chow EK