The role of STK11/LKB1 in cancer biology: implications for ovarian tumorigenesis and progression

被引:1
作者
Kang, Jian [1 ,2 ]
Gallucci, Stefano [1 ,2 ]
Pan, Junqi [1 ,2 ]
Oakhill, Jonathan S. [1 ,2 ]
Sanij, Elaine [1 ,2 ,3 ,4 ]
机构
[1] St Vincents Inst Med Res, Melbourne, Vic, Australia
[2] Univ Melbourne, St Vincents Hosp, Dept Med, Melbourne, Vic, Australia
[3] Monash Univ, Dept Biochem & Mol Biol, Melbourne, Vic, Australia
[4] Peter MacCallum Canc Ctr, Div Canc Res, Melbourne, Vic, Australia
来源
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2024年 / 12卷
基金
澳大利亚国家健康与医学研究理事会;
关键词
LKB1; STK11; cancer biology; ovarian cancer; metabolism; immunotherapy; targeted therapy; cancer signaling; PEUTZ-JEGHERS-SYNDROME; PHASE-II; LKB1; KINASE; PROTEIN; CARCINOMA; PATHWAY; GENE; LKB1/STK11; GROWTH;
D O I
10.3389/fcell.2024.1449543
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
STK11 (serine-threonine kinase 11), also known as LKB1 (liver kinase B1) is a highly conserved master kinase that regulates cellular metabolism and polarity through a complex signaling network involving AMPK and 12 other AMPK-related kinases. Germline mutations in LKB1 have been causatively linked to Peutz-Jeghers Syndrome (PJS), an autosomal dominant hereditary disease with high cancer susceptibility. The identification of inactivating somatic mutations in LKB1 in different types of cancer further supports its tumor suppressive role. Deleterious mutations in LKB1 are frequently observed in patients with epithelial ovarian cancer. However, its inconsistent effects on tumorigenesis and cancer progression suggest that its functional impact is genetic context-dependent, requiring cooperation with other oncogenic lesions. In this review, we summarize the pleiotropic functions of LKB1 and how its altered activity in cancer cells is linked to oncogenic proliferation and growth, metastasis, metabolic reprogramming, genomic instability, and immune modulation. We also review the current mechanistic understandings of this master kinase as well as therapeutic implications with particular focus on the effects of LKB1 deficiency in ovarian cancer pathogenesis. Lastly, we discuss whether LKB1 deficiency can be exploited as an Achilles heel in ovarian cancer.
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页数:16
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