Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi'an 710032, China.
Cell Signal. 2011 Aug;23(8):1235-43. doi: 10.1016/j.cellsig.2011.03.002. Epub 2011 Mar 17.
An increasing progress on the role of Hedgehog (Hh) signaling for carcinogenesis has been achieved since the link of Hh pathway to human cancer was firstly established. In particular, the critical role of Hh signaling in the development of Basal cell carcinoma (BCC) has been convincingly demonstrated by genetic mutation analyses, mouse models of BCCs, and successful clinical trials of BCCs using Hh signaling inhibitors. In addition, the Hh pathway activity is also reported to be involved in the pathogenesis of Squamous Cell Carcinoma (SCC), melanoma and Merkel Cell Carcinoma. These findings have significant new paradigm on Hh signaling transduction, its mechanisms in skin cancer and even therapeutic approaches for BCC. In this review, we will summarize the major advances in the understanding of Hh signaling transduction, the roles of Hh signaling in skin cancer development, and the current implications of "mechanism-based" therapeutic strategies.
自首次确定 Hedgehog（Hh）信号通路与人类癌症之间的联系以来，人们在 Hedgehog（Hh）信号在致癌作用方面的研究取得了不断的进展。特别是，通过遗传突变分析、基底细胞癌（BCC）的小鼠模型以及使用 Hedgehog（Hh）信号抑制剂治疗 BCC 的成功临床试验，充分证明了 Hh 信号在 BCC 发生发展中的关键作用。此外，Hh 信号通路的活性也被报道与鳞状细胞癌（SCC）、黑色素瘤和 Merkel 细胞癌的发病机制有关。这些发现为 Hedgehog（Hh）信号转导、其在皮肤癌中的机制甚至 BCC 的治疗方法提供了新的重要范例。在这篇综述中，我们将总结对 Hedgehog（Hh）信号转导的理解、Hh 信号在皮肤癌发生发展中的作用以及“基于机制”治疗策略的当前意义方面的主要进展。
