Department of Pathology, University of Ioannina Medical School, Ioannina, Greece.
Cancer Biol Ther. 2009 Nov;8(21):1986-93. doi: 10.4161/cbt.8.21.9921. Epub 2009 Nov 26.
Signaling mediated by the Notch receptor governs tissue development during embryonal organogenesis, while in adult tissues it contributes to maintenance of cellular differentiation, proliferation and apoptosis. In addition, control by the Notch pathway of stem cell self-renewal and multi-potency points to an expanding role of Notch signaling in the progression of solid tumors. Notch and its ligands are abundantly expressed in the epidermis, where Notch signaling functions as a molecular switch that intervenes in cell transition between different skin layers during the epidermal differentiation process. More recent findings obtained in melanoma and non-melanoma skin cancers show that Notch signaling has a dual action (either as an oncogene or as a tumor suppressor), depending on the tumor cell type and the synchronous activation of other intracellular signaling mechanisms. In this Review, we highlight the pleiotropic roles of the Notch signaling pathway in normal skin homeostasis and differentiation and focus on its altered regulation in the tumorigenesis of melanoma and non-melanoma skin cancer. Further understanding of the roles of Notch signaling in specific skin cancer types may provide a rationale for novel Notch-based therapeutic strategies.
Notch 受体介导的信号通路在胚胎器官发生过程中调控组织发育，而在成人组织中，它有助于维持细胞分化、增殖和凋亡。此外，Notch 通路对干细胞自我更新和多能性的控制表明 Notch 信号在实体瘤的进展中具有广泛的作用。Notch 及其配体在表皮中大量表达，在表皮分化过程中，Notch 信号作为一种分子开关，干预不同表皮层之间的细胞转换。最近在黑色素瘤和非黑色素瘤皮肤癌中获得的发现表明，Notch 信号具有双重作用（既是癌基因，也是肿瘤抑制因子），这取决于肿瘤细胞类型和其他细胞内信号机制的同步激活。在这篇综述中，我们强调了 Notch 信号通路在正常皮肤稳态和分化中的多效性作用，并重点关注其在黑色素瘤和非黑色素瘤皮肤癌发生中的改变调节。进一步了解 Notch 信号在特定皮肤癌类型中的作用可能为基于 Notch 的新型治疗策略提供依据。
