Supplementary Material for: Conservation of Epithelial-to-Mesenchymal Transition Process in Neural Crest Cells and Metastatic Cancer

Epithelial to mesenchymal transition (EMT) is a highly conserved cellular process in several species, from worms to humans. EMT plays a fundamental role in early embryogenesis, wound healing, and cancer metastasis. For neural crest cell (NCC) development, EMT typically results in forming a migratory and potent cell population that generates a wide variety of cell and tissue, including cartilage, bone, connective tissue, endocrine cells, neurons, and glia amongst many others. The degree of conservation between the signaling pathways that regulate EMT during development and metastatic cancer (MC) has not been fully established, despite ample studies. This systematic review and meta-analysis dissects the major signaling pathways involved in EMT of NCC development and MC to unravel the similarities and differences. While the FGF, TGFβ/BMP, SHH, and NOTCH pathways have been rigorously investigated in both systems, the EGF, IGF, HIPPO, Factor Receptor Superfamily, and their intracellular signaling cascades need to be the focus of future NCC studies. In general, meta-analyses of the associated signaling pathways show a significant number of overlapping genes (particularly ligands, transcription regulators, and targeted cadherins) involved in each signaling pathway of both systems without stratification by body segments and cancer type. Lack of stratification makes it difficult to meaningfully evaluate the intracellular downstream effectors of each signaling pathway. Finally, pediatric neuroblastoma and melanoma are NCC-derived malignancies, which emphasize the importance of uncovering the EMT events that convert NCC into treatment-resistant malignant cells.

上皮间质转化（Epithelial to mesenchymal transition，简称EMT）是一类在从线虫到人类的多个物种中高度保守的细胞过程。EMT在早期胚胎发生、伤口愈合以及肿瘤转移中发挥着核心作用。对于神经嵴细胞（neural crest cell，简称NCC）的发育而言，EMT通常会催生具有迁移能力的多能细胞群，该细胞群可分化产生种类丰富的细胞与组织，包括软骨、骨、结缔组织、内分泌细胞、神经元以及神经胶质细胞等诸多类型。尽管已有大量相关研究，但发育过程中调控EMT的信号通路与转移性癌症（metastatic cancer，简称MC）中调控EMT的信号通路之间的保守程度尚未完全明确。本项系统综述与荟萃分析针对NCC发育及MC中的EMT所涉及的主要信号通路展开剖析，以揭示二者的异同点。虽然FGF、TGFβ/BMP、SHH及NOTCH通路在两类系统中均已得到深入研究，但EGF、IGF、HIPPO、细胞因子受体超家族及其胞内信号级联反应仍需成为未来NCC相关研究的重点。总体而言，对相关信号通路的荟萃分析显示，在未按体节与癌症类型进行分层的情况下，两类系统的各信号通路均涉及大量重叠基因（尤其是配体、转录调控因子以及靶向钙黏蛋白）。未进行分层分析的现状使得我们难以有意义地评估各信号通路的胞内下游效应因子。最后，儿童神经母细胞瘤与黑色素瘤均为NCC起源的恶性肿瘤，这凸显了揭示将NCC转化为治疗抗性恶性细胞的EMT事件的重要性。