LKB1 inhibits telomerase activity resulting in cellular senescence through histone lactylation in lung adenocarcinoma

Liu, Mingdi; Gu, Liting; Zhang, Yuning; Li, Yunkuo; Zhang, Lihong; Xin, Ying; Wang, Yishu; Xu, Zhi-Xiang

doi:10.1016/j.canlet.2024.217025

Cited by 3 publications

(1 citation statement)

References 73 publications

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“…KRAS mutation-activated circATXN7 promotes tumor immune evasion by affecting T cell sensitivity, and lactylation plays an activating role in circATXN7, influencing the fate and function of T cells [ 22 ]. Moreover, LKB1 suppresses histone H4 lactylation, altering the activity of the transcription factor Sp1, which subsequently inhibits telomerase activity, leading to tumor cell senescence [ 23 ]. Lactylation has also been linked to proteasome inhibitor resistance.…”

Section: Introductionmentioning

confidence: 99%

The relationship and clinical significance of lactylation modification in digestive system tumors

Wang,

Zou,

Chen

et al. 2024

Cancer Cell Int

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Lactylation, an emerging post-translational modification, plays a pivotal role in the initiation and progression of digestive system tumors. This study presents a comprehensive review of lactylation in digestive system tumors, underscoring its critical involvement in tumor development and progression. By focusing on metabolic reprogramming, modulation of the tumor microenvironment, and the molecular mechanisms regulating tumor progression, the potential of targeting lactylation as a therapeutic strategy is highlighted. The research reveals that lactylation participates in gene expression regulation and cell signaling by affecting the post-translational states of histones and non-histone proteins, thereby influencing metabolic pathways and immune evasion mechanisms in tumor cells. Furthermore, this study assesses the feasibility of lactylation as a therapeutic target, providing insights for clinical treatment of gastrointestinal cancers. Future research should concentrate on elucidating the mechanisms of lactylation, developing efficient lactylation inhibitors, and validating their therapeutic efficacy in clinical trials, which could transform current cancer treatment and immunotherapy approaches. In summary, this review emphasizes the crucial role of lactylation in tumorigenesis and progression through a detailed analysis of its molecular mechanisms and clinical significance.

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Section: Introductionmentioning

confidence: 99%

The relationship and clinical significance of lactylation modification in digestive system tumors

Wang,

Zou,

Chen

et al. 2024

Cancer Cell Int

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The Annexin A1 Protein Mimetic Peptide Ac2‐26 prevents cellular senescence of CHON‐001 chondrocytes against tumor necrosis factor‐α via the Nrf2/NF‐κB pathway

Yang,

Gong,

Ren

et al. 2024

Biotech and App Biochem

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Osteoarthritis (OA) is a degenerative joint disorder characterized by progressive cartilage degradation. Excessive oxidative stress (OS), inflammatory responses, extracellular matrix breakdown, and cellular senescence of chondrocytes play crucial roles in the pathological development of OA. Currently, curing OA remains a significant challenge. In this study, we aimed to elucidate the protective effects of Annexin A1 protein Mimetic Peptide (Ac2‐26) against tumor necrosis factor‐α (TNF‐α)‐induced damage in CHON‐001 chondrocytes by assessing cellular senescence, OS, and the expression levels of matrix metalloproteinase‐13 (MMP‐13) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)‐4. Our results show that Ac2‐26 mitigated the reduction of telomerase activity and the exacerbation of cellular senescence induced by TNF‐α in CHON‐001 chondrocytes. Treatment with TNF‐α led to decreased expression of the human telomerase reverse transcriptase gene and increased expression of the telomeric repeat‐binding factor 2 gene, which were reversed by Ac2‐26 treatment. The TNF‐α‐induced increases in the gene and protein expressions of p53 and p16 were restored by Ac2‐26 in a dose‐dependent manner. Additionally, we found that TNF‐α caused elevations in the mRNA and protein levels of MMP‐13 and ADAMTS‐4, which were reduced by Ac2‐26 in a dose‐dependent fashion. Furthermore, TNF‐α triggered the activation of nuclear factor κ‐B (NF‐κB) by increasing the levels of phosphorylated NF‐κB p65 and the luciferase activity of NF‐κB. Notably, Ac2‐26 alleviated OS by reducing mitochondrial reactive oxygen species levels and promoting the activation of NF‐E2‐related factor 2 (Nrf2) in TNF‐α‐challenged CHON‐001 chondrocytes. Silencing Nrf2 abolished the Ac2‐26‐induced activation of NF‐κB and cellular senescence in CHON‐001 chondrocytes. Collectively, these findings offer new insights into the potential therapeutic use of Ac2‐26 for treating OA.

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Glis1 inhibits RTEC cellular senescence and renal fibrosis by downregulating histone lactylation in DKD

Chen,

He,

Wang

et al. 2025

Life Sciences

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LKB1 inhibits telomerase activity resulting in cellular senescence through histone lactylation in lung adenocarcinoma

Cited by 3 publications

References 73 publications

The relationship and clinical significance of lactylation modification in digestive system tumors

The relationship and clinical significance of lactylation modification in digestive system tumors

The Annexin A1 Protein Mimetic Peptide Ac2‐26 prevents cellular senescence of CHON‐001 chondrocytes against tumor necrosis factor‐α via the Nrf2/NF‐κB pathway

Glis1 inhibits RTEC cellular senescence and renal fibrosis by downregulating histone lactylation in DKD

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