LKB1 as a Tumor Suppressor in Uterine Cancer: Mouse Models and Translational Studies

The LKB1 tumor 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. The LKB1 gene 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.