Sherbet G V
School of Electrical, Electronic and Computer Engineering, University of Newcastle, Newcastle upon Tyne NE1 7RU, UK.
Cancer Lett. 2009 Jul 18;280(1):15-30. doi: 10.1016/j.canlet.2008.10.037. Epub 2008 Dec 6.
The growth, invasion and metastatic spread of cancer have been identified with the deregulation of cell proliferation, altered intercellular and cell-substratum adhesion and enhanced motility and the deposition of disseminated cancer cells at distant sites. The identification of therapeutic targets for cancer is crucial to human welfare. Drug development, molecular modelling and design of effective drugs greatly depend upon the identification of suitable therapeutic targets. Several genetic determinants relating to proliferation and growth, invasion and metastasis have been identified. S100A4 appears to be able to activate and integrate pathways to generate the phenotypic responses that are characteristic of cancer. S100A4 signalling can focus on factors associated with normal and aberrant proliferation, apoptosis and growth, and differentiation. It is able to activate signalling pathways leading to the remodelling of the cell membrane and the extracellular matrix; modulation of cytoskeletal dynamics, acquisition of invasiveness and induction of angiogenesis. Therefore S100A4 is arguably a molecular target of considerable potential possessing a wide ranging biological activity that can alter and regulate the major phenotypic features of cancer. The evolution of an appropriate strategy that permits the identification of therapeutic targets most likely to be effective in the disease process without unduly affecting normal biological processes and function is an incontrovertible imperative. By virtue of its ability to activate interacting and multi-functional signalling systems, S100A4 appears to offer suitable targets for developing new therapeutic procedures. Some effectors of the S100A4-activated pathways might also lend themselves as foci of therapeutic interest.
癌症的生长、侵袭和转移扩散与细胞增殖失调、细胞间及细胞与基质黏附的改变、运动性增强以及散在癌细胞在远处部位的沉积有关。确定癌症的治疗靶点对人类福祉至关重要。药物开发、分子建模以及有效药物的设计在很大程度上依赖于合适治疗靶点的确定。已经确定了一些与增殖和生长、侵袭和转移相关的遗传决定因素。S100A4似乎能够激活并整合多种途径,以产生癌症特有的表型反应。S100A4信号传导可聚焦于与正常和异常增殖、凋亡、生长及分化相关的因子。它能够激活导致细胞膜和细胞外基质重塑的信号通路;调节细胞骨架动力学、获得侵袭性并诱导血管生成。因此,S100A4可以说是一个具有相当潜力的分子靶点,拥有广泛的生物活性,能够改变和调节癌症的主要表型特征。制定一种合适的策略,以便在不过度影响正常生物学过程和功能的情况下,确定最有可能在疾病进程中有效的治疗靶点,这是势在必行的。凭借其激活相互作用和多功能信号系统的能力,S100A4似乎为开发新的治疗方法提供了合适的靶点。S100A4激活途径的一些效应器也可能成为治疗关注的焦点。