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

Journal article

Kang, Jian, Gallucci, Stefano, Pan, Junqi, Oakhill, Jonathan S. and Sanij, Elaine. (2024). The role of STK11/LKB1 in cancer biology : Implications for ovarian tumorigenesis and progression. Frontiers in Cell and Developmental Biology. 12, p. Article 1449543. https://doi.org/10.3389/fcell.2024.1449543
AuthorsKang, Jian, Gallucci, Stefano, Pan, Junqi, Oakhill, Jonathan S. and 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.

KeywordsLKB1; STK11; cancer biology; ovarian cancer; metabolism; immunotherapy; targeted therapy; cancer signaling
Year2024
JournalFrontiers in Cell and Developmental Biology
Journal citation12, p. Article 1449543
PublisherFrontiers Research Foundation
ISSN2296-634X
Digital Object Identifier (DOI)https://doi.org/10.3389/fcell.2024.1449543
PubMed ID39544365
Scopus EID2-s2.0-85208919746
PubMed Central IDPMC11560430
Open accessPublished as ‘gold’ (paid) open access
FunderNational Health and Medical Research Council (NHMRC)
Tour de Cure Foundation
Victorian Cancer Agency
5Point Foundation
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Open
Output statusPublished
Publication dates
Online31 Oct 2024
Publication process dates
Accepted11 Oct 2024
Deposited29 Jan 2025
Grant ID1184873
MCRF19007
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