TY - CHAP
T1 - LKB1 as a tumor suppressor in uterine cancer
T2 - Mouse models and translational studies
AU - Peña, Christopher G.
AU - Castrillón, Diego H.
N1 - Publisher Copyright:
© Springer International Publishing AG 2017.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - The LKB1 tumor suppressor was identifi ed 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.
AB - The LKB1 tumor suppressor was identifi ed 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.
KW - AMPK
KW - Endometrial cancer
KW - Genetically engineered mouse models
KW - LKB1
KW - MTOR
KW - STK11
KW - Therapeutics
KW - Uterine cancer
UR - http://www.scopus.com/inward/record.url?scp=85006013749&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85006013749&partnerID=8YFLogxK
U2 - 10.1007/978-3-319-43139-0_7
DO - 10.1007/978-3-319-43139-0_7
M3 - Chapter
C2 - 27910069
AN - SCOPUS:85006013749
T3 - Advances in Experimental Medicine and Biology
SP - 211
EP - 241
BT - Advances in Experimental Medicine and Biology
PB - Springer New York LLC
ER -