BACKGROUND In this review, we describe how the cytoskeletal protein Merlin, encoded by the Neurofibromin 2 (NF2) gene, orchestrates developmental signaling to ensure normal ontogeny, and we discuss how Merlin deficiency leads to aberrant activation of developmental pathways that enable tumor development and malignant progression. MAIN BODY Parallels between embryonic development and cancer have underscored the activation of developmental signaling pathways. Hippo, WNT/β-catenin, TGF-β, receptor tyrosine kinase (RTK), Notch, and Hedgehog pathways are key players in normal developmental biology. Unrestrained activity or loss of activity of these pathways causes adverse effects in developing tissues manifesting as developmental syndromes. Interestingly, these detrimental events also impact differentiated and functional tissues. By promoting cell proliferation, migration, and stem-cell like phenotypes, deregulated activity of these pathways promotes carcinogenesis and cancer progression. The NF2 gene product, Merlin, is a tumor suppressor classically known for its ability to induce contact-dependent growth inhibition. Merlin plays a role in different stages of an organism development, ranging from embryonic to mature states. While homozygous deletion of Nf2 in murine embryos causes embryonic lethality, Merlin loss in adult tissue is implicated in Neurofibromatosis type 2 disorder and cancer. These manifestations, cumulatively, are reminiscent of dysregulated developmental signaling. CONCLUSION Understanding the molecular and cellular repercussions of Merlin loss provides fundamental insights into the etiology of developmental disorders and cancer and has the potential, in the long term, to identify new therapeutic strategies. Video Abstract.

中文翻译：

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Merlin调节发育和癌症关系中的信号事件。

背景技术在这篇综述中，我们描述了神经纤维蛋白2（NF2）基因编码的细胞骨架蛋白Merlin如何协调发育信号以确保正常的个体发育，并且我们讨论Merlin缺乏如何导致异常激活导致肿瘤发展和恶性的发育途径。进展。主要身体胚胎发育与癌症之间的平行性强调了发育信号通路的激活。河马，WNT /β-连环蛋白，TGF-β，受体酪氨酸激酶（RTK），Notch和Hedgehog途径是正常发育生物学的关键因素。这些通路的不受约束的活动或活动丧失会导致发育中的组织出现不良反应，表现为发育综合征。有趣的是，这些有害事件也会影响分化和功能组织。通过促进细胞增殖，迁移和干细胞样表型，这些途径的活性失调可促进癌变和癌症进展。NF2基因产物Merlin是一种肿瘤抑制因子，以其诱导接触依赖性生长抑制的能力而闻名。Merlin在生物体发育的各个阶段都发挥着作用，从胚胎到成熟状态不等。虽然鼠胚胎中Nf2的纯合缺失会导致胚胎致死，但成年组织中Merlin的丢失与2型神经纤维瘤病和癌症有关。这些表现累积地使人联想到失调的发育信号。结论了解Merlin丢失的分子和细胞影响可为发育障碍和癌症的病因学提供基础见解，并具有潜在的价值，从长远来看，以确定新的治疗策略。录像摘要。