Liang Yuwei, Cao Hongliang, Tang Zhijun, Li Shuxin, Yang Gang, Dong Shuai, Du Hao, Wang Jinguo
Department of Urology II, The First Hospital of Jilin University, Changchun, China.
Front Cell Dev Biol. 2025 Aug 12;13:1629844. doi: 10.3389/fcell.2025.1629844. eCollection 2025.
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.
肝脏激酶B1（LKB1/STK11）是一种关键的肿瘤抑制因子，可调节前列腺癌（PCa）中的细胞代谢、表观遗传状态和多种信号通路。最近的研究表明，LKB1的遗传和非遗传缺失均会驱动代谢重编程、谱系可塑性和治疗抗性，主要是通过失调AMP激活的蛋白激酶（AMPK）/雷帕霉素机制靶点（mTOR）、信号转导和转录激活因子3（STAT3）以及刺猬信号通路（Hh）。本综述总结了目前关于PCa中以LKB1为中心的网络的证据，强调了LKB1失活、表观遗传重塑和侵袭性肿瘤表型之间的潜在联系。特别关注了关于LKB1和磷酸酶及张力蛋白同源物（PTEN）联合缺失对肿瘤分化影响的最新研究。最后，我们讨论了针对LKB1缺陷型PCa的代谢和表观遗传特征的新兴治疗策略，重点关注生物标志物驱动的精准医学在解决抗性和改善患者预后方面的前景。
