Institute of Genetics and Biophysics, National Research Council, 80131 Naples, Italy.
Department of Advanced Biomedical Sciences, Pathology Section, University of Naples Federico II, 80131 Naples, Italy.
Int J Mol Sci. 2020 Jan 17;21(2):607. doi: 10.3390/ijms21020607.
Early events of basal cell carcinoma (BCC) tumorigenesis are triggered by inappropriate activation of SHH signaling, via the loss of () or by activating mutations of (). TBX1 is a key regulator of pharyngeal development, mainly through expression in multipotent progenitor cells of the cardiopharyngeal lineage. This transcription factor is connected to several major signaling systems, such as FGF, WNT, and SHH, and it has been linked to cell proliferation and to the regulation of cell shape and cell dynamics. Here, we show that TBX1 was expressed in all of the 51 BCC samples that we have tested, while in healthy human skin it was only expressed in the hair follicle. Signal intensity and distribution was heterogeneous among tumor samples. Experiments performed on a cellular model of mouse BCC showed that is downstream to GLI2, a factor in the SHH signaling, and that, in turn, it regulates the expression of , which encodes an adaptor protein that is necessary for the transduction of WNT signaling. Consistently, depletion in the cellular model significantly reduced cell migration. These results suggest that TBX1 is part of a core transcription network that promotes BCC tumorigenesis.
基底细胞癌 (BCC) 肿瘤发生的早期事件是由 SHH 信号的异常激活触发的，这种异常激活是通过 () 的缺失或通过 () 的激活突变实现的。TBX1 是咽发育的关键调节因子，主要通过心咽谱系的多能祖细胞表达。这种转录因子与几个主要的信号系统有关，如 FGF、WNT 和 SHH，它与细胞增殖以及细胞形状和细胞动力学的调节有关。在这里，我们表明，TBX1 在我们测试的 51 个 BCC 样本中均有表达，而在健康的人类皮肤中，它仅在毛囊中表达。肿瘤样本中的信号强度和分布存在异质性。在小鼠 BCC 的细胞模型上进行的实验表明，是 SHH 信号传导中的因子 GLI2 的下游，而它反过来又调节编码衔接蛋白的 的表达，该蛋白是 WNT 信号传导所必需的。一致地，细胞模型中的 耗竭显著降低了细胞迁移。这些结果表明，TBX1 是促进 BCC 肿瘤发生的核心转录网络的一部分。
