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REVIEW article

Front. Cell Dev. Biol.
Sec. Cell Growth and Division
Volume 12 - 2024 | doi: 10.3389/fcell.2024.1449543
This article is part of the Research Topic Proceedings from ACDTM 2023: Cell Cycle, DNA Repair, and Telomeres View all 4 articles

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

Provisionally accepted
Jian Kang Jian Kang *Stefano Gallucci Stefano Gallucci Junqi Pan Junqi Pan Jon Oakhill Jon Oakhill Elaine Sanij Elaine Sanij
  • St Vincents Institute of Medical Research, University of Melbourne, Fitzroy, Australia

The final, formatted version of the article will be published soon.

    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

    Received: 15 Jun 2024; Accepted: 11 Oct 2024.

    Copyright: © 2024 Kang, Gallucci, Pan, Oakhill and Sanij. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jian Kang, St Vincents Institute of Medical Research, University of Melbourne, Fitzroy, Australia

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.