The bright and the dark sides of activin in wound healing and cancer
The bright and the dark sides of activin in wound healing and cancer
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DOI：
10.1242/jcs.094789
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发表时间：
2012-09-01
影响因子：
4
通讯作者：
Werner, Sabine
中科院分区：
文献类型：
--
作者：
Antsiferova, Maria;Werner, Sabine
激活素最初被描述为刺激垂体释放促卵泡激素的蛋白质，并且众所周知其在不同生殖功能中的重要作用。近年来，随着激活素在血管生成、炎症、免疫、纤维化和癌症中的新功能的发现，这种多功能因子引起了其他领域研究人员的注意。我们实验室的研究已经确定激活素是伤口愈合和皮肤致癌的关键调节剂。一方面，它强烈加速皮肤伤口的愈合过程，但另一方面，它增强了疤痕形成和皮肤肿瘤发生的易感性。最后，来自几个实验室的结果表明，激活素增强了其他一些器官中的肿瘤形成和/或进展，特别是通过其对肿瘤微环境的影响，并且它还促进了癌症引起的骨破坏和肌肉萎缩。这些发现提供了使用激活素或其下游靶标改善受损的伤口愈合以及使用激活素拮抗剂预防和治疗纤维化和过表达激活素的恶性肿瘤的基础。在这里，我们总结了以前所描述的激活素在伤口愈合和瘢痕形成的作用，并讨论了功能研究，揭示了不同的功能激活素在癌症的发病机制。这些研究结果的临床应用的相关性将得到强调。
Activin was initially described as a protein that stimulates release of follicle stimulating hormone from the pituitary, and it is well known for its important roles in different reproductive functions. In recent years, this multifunctional factor has attracted the attention of researchers in other fields, as new functions of activin in angiogenesis, inflammation, immunity, fibrosis and cancer have been discovered. Studies from our laboratory have identified activin as a crucial regulator of wound healing and skin carcinogenesis. On the one hand, it strongly accelerates the healing process of skin wounds but, on the other hand, it enhances scar formation and the susceptibility to skin tumorigenesis. Finally, results from several laboratories have revealed that activin enhances tumour formation and/or progression in some other organs, in particular through its effect on the tumour microenvironment, and that it also promotes cancer-induced bone disruption and muscle wasting. These findings provide the basis for the use of activin or its downstream targets for the improvement of impaired wound healing, and of activin antagonists for the prevention and treatment of fibrosis and of malignant tumours that overexpress activin. Here, we summarize the previously described roles of activin in wound healing and scar formation and discuss functional studies that revealed different functions of activin in the pathogenesis of cancer. The relevance of these findings for clinical applications will be highlighted.