Oncometabolite lactate enhances breast cancer progression by orchestrating histone lactylation-dependent c-Myc expression

Pandkar, Madhura R.; Sinha, Sommya; Samaiya, Atul; Shukla, Sanjeev

doi:10.1016/j.tranon.2023.101758

Cited by 9 publications

(3 citation statements)

References 70 publications

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“…For example, compared to normal cells, the ocular melanoma cells have elevated levels of lactylation, thereby favoring tumor development, and the inhibition of lactylation levels can inhibit tumor development [ 18 ]. A similar phenomenon was also reported in tumors, such as hepatocellular carcinoma [ 50 ] and breast cancer [ 51 , 52 ].…”

Section: Discussionsupporting

confidence: 78%

Proanthocyanidins Ameliorate LPS-Inhibited Osteogenesis of PDLSCs by Restoring Lysine Lactylation

Wu,

Wang,

Zhang

et al. 2024

IJMS

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Periodontitis is a bacteria-induced inflammatory disease characterized by the progressive destruction of periodontal supporting tissues. Periodontal ligament stem cells (PDLSCs) are capable of differentiating into osteoblasts, which is an important stem cell source for endogenous periodontal tissue regeneration. Lysine lactylation (Kla) is a novel post-translational modification of proteins that is recently thought to be associated with osteogenic differentiation. Here, we found that lactylation levels are reduced both in the periodontal tissue of rats with periodontitis and lipopolysaccharide (LPS)-stimulated human PDLSCs. Proanthocyanidins were able to promote the osteogenesis of inflamed PDLSCs by restoring lactylation levels. Mechanistically, proanthocyanidins increased lactate production and restored the lactylation levels of PDLSCs, which recovered osteogenesis of inflamed PDLSCs via the Wnt/β-catenin pathway. These results provide evidence on how epigenetic regulation by pharmacological agents influence the osteogenic phenotype of stem cells and the process of periodontal tissue repair. Our current study highlights the valuable potential of natural product proanthocyanidins in the regenerative engineering of periodontal tissues.

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Section: Discussionsupporting

confidence: 78%

Proanthocyanidins Ameliorate LPS-Inhibited Osteogenesis of PDLSCs by Restoring Lysine Lactylation

Wu,

Wang,

Zhang

et al. 2024

IJMS

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“…[17][18][19] Examining histone lactylation provides a thorough analysis of the latest advancements in researching this alteration in cancer, particularly emphasising its effects on reshaping tumour characteristics, regulating gene activity, promoting glycolysis in cancer stem cells and impacting the tumour's immune microenvironment (Figure 1). [20][21][22]…”

Section: Introductionmentioning

confidence: 99%

Histone lactylation bridges metabolic reprogramming and epigenetic rewiring in driving carcinogenesis: Oncometabolite fuels oncogenic transcription

Zhang,

Song,

et al. 2024

Clinical & Translational Med

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Heightened lactate production in cancer cells has been linked to various cellular mechanisms such as angiogenesis, hypoxia, macrophage polarisation and T‐cell dysfunction. The lactate‐induced lactylation of histone lysine residues is noteworthy, as it functions as an epigenetic modification that directly augments gene transcription from chromatin. This epigenetic modification originating from lactate effectively fosters a reliance on transcription, thereby expediting tumour progression and development. Herein, this review explores the correlation between histone lactylation and cancer characteristics, revealing histone lactylation as an innovative epigenetic process that enhances the vulnerability of cells to malignancy. Moreover, it is imperative to acknowledge the paramount importance of acknowledging innovative therapeutic methodologies for proficiently managing cancer by precisely targeting lactate signalling. This comprehensive review illuminates a crucial yet inadequately investigated aspect of histone lactylation, providing valuable insights into its clinical ramifications and prospective therapeutic interventions centred on lactylation.

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“…Besides, Lactylation promotes DNA damage repair and chemoresistance ( Chen et al, 2024 ). It has been reported that the occurrence and progression of a variety of tumors, such as liver cancer ( Gu et al, 2022 ; Kotsiliti, 2023 ), breast cancer ( Deng and Liao, 2023 ; Pandkar et al, 2023 ), colorectal cancer ( Li et al, 2023 ; Zhou et al, 2023 ), etc., all play an important role. In prostate cancer, histone lactylation affects cancer cell plasticity and leads to transcriptional surges of neuroendocrine genes ( He et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Constructing lactylation-related genes prognostic model to effectively predict the disease-free survival and treatment responsiveness in prostate cancer based on machine learning

Pan,

Zhang,

Lin

et al. 2024

Front. Genet.

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Background: Prostate cancer (PCa) is one of the most common malignancies in men with a poor prognosis. It is therefore of great clinical importance to find reliable prognostic indicators for PCa. Many studies have revealed the pivotal role of protein lactylation in tumor development and progression. This research aims to analyze the effect of lactylation-related genes on PCa prognosis.Methods: By downloading mRNA-Seq data of TCGA PCa, we obtained the differential genes related to lactylation in PCa. Five machine learning algorithms were used to screen for lactylation-related key genes for PCa, then the five overlapping key genes were used to construct a survival prognostic model by lasso cox regression analysis. Furthermore, the relationships between the model and related pathways, tumor mutation and immune cell subpopulations, and drug sensitivity were explored. Moreover, two risk groups were established according to the risk score calculated by the five lactylation-related genes (LRGs). Subsequently, a nomogram scoring system was established to predict disease-free survival (DFS) of patients by combining clinicopathological features and lactylation-related risk scores. In addition, the mRNA expression levels of five genes were verified in PCa cell lines by qPCR.Results: We identified 5 key LRGs (ALDOA, DDX39A, H2AX, KIF2C, RACGAP1) and constructed the LRGs prognostic model. The AUC values for 1 -, 3 -, and 5-year DFS in the TCGA dataset were 0.762, 0.745, and 0.709, respectively. The risk score was found a better predictor of DFS than traditional clinicopathological features in PCa. A nomogram that combined the risk score with clinical variables accurately predicted the outcome of the patients. The PCa patients in the high-risk group have a higher proportion of regulatory T cells and M2 macrophage, a higher tumor mutation burden, and a worse prognosis than those in the low-risk group. The high-risk group had a lower IC50 for certain chemotherapeutic drugs, such as Docetaxel, and Paclitaxel than the low-risk group. Furthermore, five key LRGs were found to be highly expressed in castration-resistant PCa cells.Conclusion: The lactylation-related genes prognostic model can effectively predict the DFS and therapeutic responses in patients with PCa.

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Oncometabolite lactate enhances breast cancer progression by orchestrating histone lactylation-dependent c-Myc expression

Cited by 9 publications

References 70 publications

Proanthocyanidins Ameliorate LPS-Inhibited Osteogenesis of PDLSCs by Restoring Lysine Lactylation

Proanthocyanidins Ameliorate LPS-Inhibited Osteogenesis of PDLSCs by Restoring Lysine Lactylation

Histone lactylation bridges metabolic reprogramming and epigenetic rewiring in driving carcinogenesis: Oncometabolite fuels oncogenic transcription

Constructing lactylation-related genes prognostic model to effectively predict the disease-free survival and treatment responsiveness in prostate cancer based on machine learning

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