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捕捞肠道癌模型:揭示斑马鱼胃肠道稳态和肿瘤发生的机制。

Fishing for intestinal cancer models: unraveling gastrointestinal homeostasis and tumorigenesis in zebrafish.

机构信息

Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, The Netherlands.

出版信息

Zebrafish. 2009 Dec;6(4):361-76. doi: 10.1089/zeb.2009.0617.

DOI:10.1089/zeb.2009.0617
PMID:19929219
Abstract

Zebrafish has proven to be a highly versatile model for comprehensive studies of gene function in development. Given that the molecular pathways involved in epithelial carcinogenesis appear to be conserved across vertebrates, zebrafish is now considered as a valid model to study tumor biology. Development and homeostasis in multicellular organisms are dependent on a complex interplay between cell proliferation, migration, differentiation, and cell death. The Wnt signaling pathway is a major signaling pathway during embryonic development and is the key regulator of self-renewal homeostasis in several adult tissues. A large body of knowledge on adult stem-cell biology has arisen from the study of the intestinal epithelium over the past 20 years. The Wnt pathway has appeared as its principal regulator of homeostatic self-renewal. Moreover, most cancers of the intestine are caused by activating mutations in the Wnt pathway. Recently, zebrafish models have been developed to study Wnt pathway-induced cancer. An appealing avenue for cancer research in zebrafish is large-scale screens to identify chemotherapeutic and chemopreventive agents in conjunction with the in vivo imaging approaches that zebrafish affords.

摘要

斑马鱼已被证明是一种非常通用的模型,可用于全面研究发育过程中的基因功能。鉴于涉及上皮癌发生的分子途径似乎在脊椎动物中是保守的,因此斑马鱼现在被认为是研究肿瘤生物学的有效模型。多细胞生物的发育和稳态依赖于细胞增殖、迁移、分化和细胞死亡之间的复杂相互作用。Wnt 信号通路是胚胎发育过程中的主要信号通路,是几个成年组织中自我更新稳态的关键调节剂。过去 20 年来,对肠道上皮的研究产生了大量关于成体干细胞生物学的知识。Wnt 途径已成为其稳态自我更新的主要调节剂。此外,肠道的大多数癌症是由 Wnt 途径中的激活突变引起的。最近,已经开发出斑马鱼模型来研究 Wnt 途径诱导的癌症。斑马鱼癌症研究的一个有吸引力的途径是进行大规模筛选,以结合斑马鱼提供的体内成像方法来识别化疗和化学预防药物。

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