Central Laboratory, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei, China.
Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, Guangdong, China.
Biomed Environ Sci. 2024 Jul 20;37(7):774-784. doi: 10.3967/bes2024.095.
Melanocytes derived from neural crest cells harbor the BRAF mutation, which is the predominant driver of nevus formation in humans. This mutation leads to malignant cell proliferation and subsequent cell cycle arrest, culminating in oncogene-induced senescence and nevus development. Nevertheless, emerging evidence has highlighted the heterogeneity of cellular senescence markers in BRAF -induced senescent melanocytes. Moreover, the capacity of melanocytes within nevi to regain their proliferative ability raises questions about the molecular mechanisms by which BRAF , the mitogen-activated protein kinase signaling pathway, triggers nevus formation. This study provides an overview and discussion of the molecular mechanisms underpinning BRAF -induced melanocyte nevus formation and the relevant animal models employed for their elucidation. It also highlights the significance of elucidating dynamic changes in cytoplasmic and nuclear substrates that interact with phosphorylated extracellular signal-regulated protein kinases 1 and 2 and underscores the value of using targeted BRAF animal models created through gene editing technologies.
黑素细胞来源于神经嵴细胞，携带 BRAF 突变，这是人类痣形成的主要驱动因素。该突变导致恶性细胞增殖和随后的细胞周期停滞，最终导致癌基因诱导的衰老和痣的发展。然而，新出现的证据强调了 BRAF 诱导的衰老黑素细胞中细胞衰老标志物的异质性。此外，痣内黑素细胞恢复增殖能力的能力引发了关于 BRAF （丝裂原活化蛋白激酶信号通路）触发痣形成的分子机制的问题。本研究提供了一个概述和讨论 BRAF 诱导的黑素细胞痣形成的分子机制以及用于阐明这些机制的相关动物模型。它还强调了阐明与磷酸化细胞外信号调节蛋白激酶 1 和 2 相互作用的细胞质和核底物的动态变化的重要性，并强调了使用通过基因编辑技术创建的靶向 BRAF 动物模型的价值。
