Institute of Pathology , Ludwig-Maximilians University, Thalkirchnerstr. 36, DE-80337 Munich, Germany.
Acta Derm Venereol. 2019 Jan 1;99(1):63-71. doi: 10.2340/00015555-3031.
Deregulated Hedgehog signalling is a driver of basal cell carcinomas. One effector of the Hedgehog pathway is n-MYC. c/n-MYC proteins, NAMPT and DBC1 are linked to SIRT1 in a positive feedback loop that may contribute to tumorigenesis of basal cell carcinoma. In 5 basal cell carcinoma types immunohistochemistry revealed n-MYC, NAMPT and SIRT1 expression. DBC1 was homogenously expressed in all epithelial cells. NAMPT, SIRT1 and c-MYC were expressed in the stratum basale of human and murine skin. In hair follicles NAMPT and SIRT1 were expressed together with c-MYC and n-MYC, except for the matrix, where n-MYC was strongly positive, but c-MYC expression was absent. Therefore, a common pathway connecting n-MYC, NAMPT and SIRT1 may be active in basal cell carcinomas and in their cells of origin. This pathway may contribute to the development of basal cell carcinomas. Targeting factors in the feedback loop may offer novel therapeutic options.
Hedgehog 信号通路失调是基底细胞癌的驱动因素之一。Hedgehog 通路的一个效应物是 n-MYC。c/n-MYC 蛋白、NAMPT 和 DBC1 与 SIRT1 形成正反馈回路，这可能有助于基底细胞癌的发生。在 5 种基底细胞癌类型中，免疫组织化学显示 n-MYC、NAMPT 和 SIRT1 的表达。DBC1 在所有上皮细胞中均匀表达。NAMPT、SIRT1 和 c-MYC 在人和鼠皮肤的基底层表达。在毛囊中，NAMPT 和 SIRT1 与 c-MYC 和 n-MYC 一起表达，除了基质，那里 n-MYC 强阳性，但 c-MYC 表达缺失。因此，连接 n-MYC、NAMPT 和 SIRT1 的共同途径可能在基底细胞癌及其起源细胞中活跃。该途径可能有助于基底细胞癌的发展。靶向反馈回路中的因子可能提供新的治疗选择。
