LKB1 as a Tumor Suppressor in Uterine Cancer: Mouse Models and Translational Studies.
LKB1 as a Tumor Suppressor in Uterine Cancer: Mouse Models and Translational Studies.
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DOI：
10.1007/978-3-319-43139-0_7
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发表时间：
2017
影响因子：
--
通讯作者：
C. G. Peña;D. Castrillon
中科院分区：
文献类型：
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作者：
C. G. Peña;D. Castrillon
LKB1抑癌基因于1998年被鉴定为Peutz-Jeghers综合征(PJS)中的突变基因，PJS是一种遗传性癌症易感性，以胃肠道息肉和各种解剖部位的癌症，特别是癌症的高发病率为特征，包括胃肠道、肺部和女性生殖道。患有PJS的妇女子宫体(子宫内膜)和子宫颈癌的发病率很高。在发生在这些位置的人类癌症中，LKB1基因也发生了体细胞突变。在小鼠模型上的研究强调了LKB1作为子宫内膜肿瘤抑制因子的效力，以及它在推动侵袭和转移生长方面的独特作用。这些体内模型代表了易于处理的实验系统，用于在肿瘤发生的背景下发现潜在的生物学原理和由LKB1调控的分子过程，也可以作为实验治疗学的有用的临床前模型系统。在这里，我们回顾了LKB1的S在mTOR信号、代谢和细胞极性中的已知角色，重点介绍了与子宫癌发生相关的人类病理学和小鼠模型，包括子宫体和子宫颈癌。
TheLKB1tumor suppressor was identified in 1998 as the gene mutated in the Peutz–Jeghers Syndrome (PJS), a hereditary cancer predisposition characterized by gastrointestinal polyposis and a high incidence of cancers, particularly carcinomas, at a variety of anatomic sites including the gastrointestinal tract, lung, and female reproductive tract. Women with PJS have a high incidence of carcinomas of the uterine corpus (endometrium) and cervix. TheLKB1gene is also somatically mutated in human cancers arising at these sites. Work in mouse models has highlighted the potency of LKB1 as an endometrial tumor suppressor and its distinctive roles in driving invasive and metastatic growth. These in vivo models represent tractable experimental systems for the discovery of underlying biological principles and molecular processes regulated by LKB1 in the context of tumorigenesis and also serve as useful preclinical model systems for experimental therapeutics. Here we review LKB1’s known roles in mTOR signaling, metabolism, and cell polarity, with an emphasis on human pathology and mouse models relevant to uterine carcinogenesis, including cancers of the uterine corpus and cervix.