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The role of STK11/LKB1 in cancer biology : Implications for ovarian tumorigenesis and progression
Kang, Jian Gallucci, Stefano Pan, Junqi Oakhill, Jonathan S. Sanij, Elaine
Kang, Jian
Gallucci, Stefano
Pan, Junqi
Oakhill, Jonathan S.
Sanij, Elaine
Abstract
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.
Keywords
LKB1, STK11, cancer biology, ovarian cancer, metabolism, immunotherapy, targeted therapy, cancer signaling
Date
2024
Type
Journal article
Journal
Frontiers in Cell and Developmental Biology
Book
Volume
12
Issue
Page Range
Article Number
Article 1449543
ACU Department
Non-faculty
Collections
Files
Relation URI
Source URL
Event URL
Open Access Status
Published as ‘gold’ (paid) open access
License
CC BY 4.0
File Access
Open