Liu Jianglan, Fukunaga-Kalabis Mizuho, Li Ling, Herlyn Meenhard
Molecular and Cellular Oncogenesis Program, Melanoma Research Center, The Wistar Institute, Philadelphia, USA.
Molecular and Cellular Oncogenesis Program, Melanoma Research Center, The Wistar Institute, Philadelphia, USA.
Arch Biochem Biophys. 2014 Dec 1;563:13-21. doi: 10.1016/j.abb.2014.07.023. Epub 2014 Aug 8.
Cutaneous malignant melanomas originate primarily within epidermal melanocytic cells. Melanoma cells share many characteristics with melanocyte precursors, suggesting that melanoma cells utilize the developmental programs of their normal counterpart for their own progression. The pigmentation system provides an advantageous model to assess survival pathway interactions in the melanocytic lineage, as genetic alterations controlling melanocyte development can be easily detectable by coat color phenotype that do not affect the viability of an animal. By integrating combinatorial gene knockout approaches, cell-based assays and immunohistochemical observations, recent studies have illustrated several genes and pathways that play important roles both in melanocyte specification and maintenance and in melanoma formation and progression. We are reviewing those genes and pathways to understand the connection between normal and cancerous development and to reveal therapeutic potential of targeting developmental pathways for melanoma therapy.
皮肤恶性黑色素瘤主要起源于表皮黑素细胞。黑色素瘤细胞与黑素细胞前体具有许多共同特征，这表明黑色素瘤细胞利用其正常对应物的发育程序来实现自身进展。色素沉着系统为评估黑素细胞谱系中的生存途径相互作用提供了一个有利模型，因为控制黑素细胞发育的基因改变可以通过不影响动物生存能力的毛色表型轻易检测到。通过整合组合基因敲除方法、基于细胞的检测和免疫组织化学观察，最近的研究已经阐明了几个在黑素细胞的特化和维持以及黑色素瘤的形成和进展中都起重要作用的基因和途径。我们正在综述这些基因和途径，以了解正常发育与癌症发育之间的联系，并揭示靶向发育途径用于黑色素瘤治疗的治疗潜力。
