The role of LKB1 in prostate cancer: implications for tumor progression and therapy

Liver kinase B1 (LKB1/STK11) is a key tumor suppressor that regulates cellular metabolism, epigenetic states, and multiple signaling pathways in prostate cancer (PCa). Recent studies reveal that both genetic and non-genetic LKB1 loss drives metabolic reprogramming, lineage plasticity, and treatment...

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Main Authors: Yuwei Liang, Hongliang Cao, Zhijun Tang, Shuxin Li, Gang Yang, Shuai Dong, Hao Du, Jinguo Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2025.1629844/full
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author Yuwei Liang
Hongliang Cao
Zhijun Tang
Shuxin Li
Gang Yang
Shuai Dong
Hao Du
Jinguo Wang
author_facet Yuwei Liang
Hongliang Cao
Zhijun Tang
Shuxin Li
Gang Yang
Shuai Dong
Hao Du
Jinguo Wang
author_sort Yuwei Liang
collection DOAJ
description Liver kinase B1 (LKB1/STK11) is a key tumor suppressor that regulates cellular metabolism, epigenetic states, and multiple signaling pathways in prostate cancer (PCa). Recent studies reveal that both genetic and non-genetic LKB1 loss drives metabolic reprogramming, lineage plasticity, and treatment resistance, mainly through dysregulation of the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT3), and Hedgehog (Hh) pathways. This review summarizes current evidence on LKB1-centered networks in PCa, highlighting the potential link between LKB1 inactivation, epigenetic remodeling, and aggressive tumor phenotypes. Special attention is given to recent studies on the impact of combined LKB1 and Phosphatase and Tensin Homolog (PTEN) loss on tumor differentiation. Finally, we discuss emerging therapeutic strategies aimed at the metabolic and epigenetic features of LKB1-deficient PCa, with a focus on the prospects for biomarker-driven precision medicine to address resistance and improve patient outcomes.
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spelling doaj-art-b52b1f9931bc4ffe8b303a3b109c7f6d2025-08-20T04:02:31ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-08-011310.3389/fcell.2025.16298441629844The role of LKB1 in prostate cancer: implications for tumor progression and therapyYuwei LiangHongliang CaoZhijun TangShuxin LiGang YangShuai DongHao DuJinguo WangLiver kinase B1 (LKB1/STK11) is a key tumor suppressor that regulates cellular metabolism, epigenetic states, and multiple signaling pathways in prostate cancer (PCa). Recent studies reveal that both genetic and non-genetic LKB1 loss drives metabolic reprogramming, lineage plasticity, and treatment resistance, mainly through dysregulation of the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT3), and Hedgehog (Hh) pathways. This review summarizes current evidence on LKB1-centered networks in PCa, highlighting the potential link between LKB1 inactivation, epigenetic remodeling, and aggressive tumor phenotypes. Special attention is given to recent studies on the impact of combined LKB1 and Phosphatase and Tensin Homolog (PTEN) loss on tumor differentiation. Finally, we discuss emerging therapeutic strategies aimed at the metabolic and epigenetic features of LKB1-deficient PCa, with a focus on the prospects for biomarker-driven precision medicine to address resistance and improve patient outcomes.https://www.frontiersin.org/articles/10.3389/fcell.2025.1629844/fullLKB1prostate cancersignaling pathway regulationepigenetic regulationprecision therapeutic targets
spellingShingle Yuwei Liang
Hongliang Cao
Zhijun Tang
Shuxin Li
Gang Yang
Shuai Dong
Hao Du
Jinguo Wang
The role of LKB1 in prostate cancer: implications for tumor progression and therapy
Frontiers in Cell and Developmental Biology
LKB1
prostate cancer
signaling pathway regulation
epigenetic regulation
precision therapeutic targets
title The role of LKB1 in prostate cancer: implications for tumor progression and therapy
title_full The role of LKB1 in prostate cancer: implications for tumor progression and therapy
title_fullStr The role of LKB1 in prostate cancer: implications for tumor progression and therapy
title_full_unstemmed The role of LKB1 in prostate cancer: implications for tumor progression and therapy
title_short The role of LKB1 in prostate cancer: implications for tumor progression and therapy
title_sort role of lkb1 in prostate cancer implications for tumor progression and therapy
topic LKB1
prostate cancer
signaling pathway regulation
epigenetic regulation
precision therapeutic targets
url https://www.frontiersin.org/articles/10.3389/fcell.2025.1629844/full
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