文章：

原癌基因MYC驱动人类黑素细胞黑色素生成和衰老

Protooncogene MYC drives human melanocyte melanogenesis and senescence 

原文发布日期：2022-01-12 

英文摘要：

In spite of extensive research and advances on the molecular biology of melanoma, the process of melanocytic differentiation or its relationship with proliferation is poorly understood. The role of proto-oncogenes in normal melanocyte biology is also intriguing. Proto-oncogene MYC is overexpressed in 40% of melanomas. It has been suggested that MYC can mediate senescence bypass in malignant melanocytes, an important event in melanoma development, likely in cooperation with other oncogenic pathways. However, despite the apparent importance of MYC in melanoma, its functions in normal melanocytes are unknown. We have overexpressed MYC in freshly isolated human primary melanocytes and studied the effects on melanocytic proliferation and differentiation. MYC promoted a transient activation of melanocytes including cell cycle entry, DNA damage and cell migration. Subsequently, MYC induced melanogenesis, increased cellular size and complexity and senescence. Interestingly, we also found strong expression of MYC in regions of human nevi displaying high pigmentation and high expression of senescence marker p16. The results altogether show that MYC drives melanocytic differentiation and suggest that senescence is associated with differentiation. We discuss the implications into the mechanisms governing melanocytic differentiation and the development of melanoma. 

摘要翻译： 

尽管对黑色素瘤的分子生物学进行了广泛研究并取得了进展，但人们对黑色素细胞分化过程及其与增殖的关系仍知之甚少。原癌基因在正常黑色素细胞生物学中的作用也令人关注。原癌基因MYC在40%的黑色素瘤中过度表达。有研究表明，MYC可能与其他致癌通路协同作用，介导恶性黑色素细胞衰老逃逸——这是黑色素瘤发展中的重要事件。然而，尽管MYC在黑色素瘤中具有明显重要性，但其在正常黑色素细胞中的功能尚不明确。我们在新鲜分离的人原代黑色素细胞中过表达MYC，并研究其对黑色素细胞增殖和分化的影响。MYC促进了黑色素细胞的瞬时激活，包括细胞周期进入、DNA损伤和细胞迁移。随后，MYC诱导了黑色素生成，增加细胞体积和复杂性，并引发衰老。有趣的是，我们还在人类痣组织色素沉着区域和衰老标志物p16高表达区域发现了MYC的强表达。这些结果表明MYC驱动黑色素细胞分化，并提示衰老与分化相关。我们进一步探讨了这一发现对黑色素细胞分化调控机制及黑色素瘤发展的意义。

原文链接：

Protooncogene MYC drives human melanocyte melanogenesis and senescence