Dysregulated molecular networks in head and neck carcinogenesis.

Dysregulated molecular networks in head and neck carcinogenesis.
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DOI:
10.1016/j.oraloncology.2008.07.011
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发表时间:
2009-04
期刊:
影响因子:
4.8
通讯作者:
Gutkind, J. Silvio
Gutkind, J. Silvio
中科院分区:
医学2区
文献类型:
--
作者:
Molinolo, Alfredo A.;Amornphimoltham, Panomwat;Squarize, Cristiane H.;Castilho, Rogerio M.;Patel, Vyomesh;Gutkind, J. Silvio

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多种遗传和表观遗传事件,包括调节细胞信号传导、生长、存活、运动、血管生成和细胞周期控制的分子的异常表达和功能,是头颈部鳞状细胞癌(HNSCC)恶性表型进行性获得的基础。在这方面,最近我们对细胞外组分、细胞表面分子和无数细胞内蛋白质和第二信使系统如何相互作用,以及如何组织成通路和网络以控制细胞和组织功能以及细胞命运决定的理解有了很大的发展。这种理解控制细胞间和细胞内通讯的基本机制的能力为理解它们的失调如何促进人类癌症的生长和传播提供了前所未有的机会。在这里,我们将讨论如何使用现代技术的新兴信息,包括基因阵列和蛋白质组学研究,结合异常信号网络的分子解剖,包括EGFR,ras,NFκB,Stat,Wnt/β-catenin,TGF-β和PI 3 K-AKT-mTOR信号通路,可以帮助阐明HNSCC进展的分子机制。最终,我们可以设想,这方面的知识可能会提供巨大的机会,癌前鳞状病变的诊断,并为预防和治疗HNSCC的新的分子靶向策略的发展。
Multiple genetic and epigenetic events, including the aberrant expression and function of molecules regulating cell signaling, growth, survival, motility, angiogenesis, and cell cycle control, underlie the progressive acquisition of a malignant phenotype in squamous carcinomas of the head and neck (HNSCC). In this regard, there has been a recent explosion in our understanding on how extracellular components, cell surface molecules, and a myriad of intracellular proteins and second messenger systems interact with each other, and are organized in pathways and networks to control cellular and tissue functions and cell fate decisions. This emerging ability to understand the basic mechanism controlling inter- and intra-cellular communication has provided an unprecedented opportunity to understand how their dysregulation contributes to the growth and dissemination of human cancers. Here, we will discuss the emerging information on how the use of modern technologies, including gene array and proteomic studies, combined with the molecular dissection of aberrant signaling networks, including the EGFR, ras, NFκB, Stat, Wnt/β-catenin, TGF-β, and PI3K-AKT-mTOR signaling pathways, can help elucidate the molecular mechanisms underlying HNSCC progression. Ultimately, we can envision that this knowledge may provide tremendous opportunities for the diagnosis of premalignant squamous lesions, and for the development of novel molecular-targeted strategies for the prevention and treatment of HNSCC.
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