Martinez-Barbera Juan Pedro
Developmental Biology and Cancer ProgrammeInstitute of Child Health, Birth Defects Research Centre, University College London, 30 Guilford Street, WC1N 1EH London, UK
J Endocrinol. 2015 Aug;226(2):T161-72. doi: 10.1530/JOE-15-0145. Epub 2015 Apr 29.
Adamantinomatous craniopharyngiomas (ACP) are clinically relevant tumours that are associated with high morbidity, poor quality of life and occasional mortality. Human and mouse studies have provided important insights into the biology of these aggressive tumours, and we are starting to understand why, how and when these tumours develop in humans. Mutations in β-catenin that result in the over-activation of the WNT/β-catenin signalling pathway are critical drivers of most, perhaps of all, human ACPs. Mouse studies have shown that only pituitary embryonic precursors or adult stem cells are able to generate tumours when targeted with oncogenic β-catenin, which suggests that the cell context is critical in order for mutant β-catenin to exert its oncogenic effect. Interestingly, mutant stem cells do not generate the bulk of the tumour cells; instead, they induce tumours in a paracrine manner. Combining basic studies in mice and humans will provide further insights into the biology of these neoplasms and will reveal pathogenic pathways that could be targeted with specific inhibitors for the benefit of patients. These benign tumours may additionally represent a unique model for investigating the early steps that lead to oncogenesis.
成釉细胞瘤型颅咽管瘤（ACP）是具有临床相关性的肿瘤，与高发病率、生活质量差及偶发死亡率相关。人和小鼠研究为这些侵袭性肿瘤的生物学特性提供了重要见解，我们也开始了解这些肿瘤在人类体内为何、如何以及何时发生。β-连环蛋白的突变导致WNT/β-连环蛋白信号通路过度激活，是大多数（或许是所有）人类ACP的关键驱动因素。小鼠研究表明，只有垂体胚胎前体细胞或成体干细胞在受到致癌性β-连环蛋白作用时能够生成肿瘤，这表明细胞环境对于突变型β-连环蛋白发挥致癌作用至关重要。有趣的是，突变干细胞并不会产生大部分肿瘤细胞；相反，它们以旁分泌方式诱导肿瘤形成。将小鼠和人类的基础研究相结合，将为这些肿瘤的生物学特性提供进一步见解，并揭示可通过特定抑制剂靶向作用的致病途径，从而造福患者。这些良性肿瘤还可能代表了一个用于研究肿瘤发生早期步骤的独特模型。
