Rewired glycolysis by DTL accelerates oncometabolite L-lactate generation to promote breast cancer progression DOI Creative Commons
Yuhao Liu, Jinting Li, Yiren Cao

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: May 5, 2025

Breast cancer (BC) has become the leading cause of global incidence. Despite therapeutic advances, a critical unmet need persists for identifying novel targets. Our integrated bioinformatics analysis identified DTL, component Cullin-RING ligase (CRL) E3 ubiquitin family, as significantly upregulated in BC tissues. This upregulation correlated with poor patient prognosis, stemness, and metabolic reprogramming, which was driven by genetic alterations such gene amplification reduced promoter methylation. Functional studies demonstrated that DTL promoted breast cell proliferation migration vitro through glycolysis remodeling. Mechanistically, positively regulated key glycolytic enzymes (HK2, ENO1, PKM2, LDHA) independently its canonical activity directly interacted LDHA. Notably, exogenous L-lactate enhanced tumor growth metastasis. Collectively, our findings reveal non-canonical mechanism whereby drives to generate oncometabolite L-lactate, sustains malignancy independent protein degradation. The strong association between adverse clinical outcomes, coupled multifaceted regulatory roles biology, highlighting potential target BC.

Language: Английский

Lactylation in health and disease: physiological or pathological? DOI Creative Commons
Lijun Zhao,

Haonan Qi,

Huiying Lv

et al.

Theranostics, Journal Year: 2025, Volume and Issue: 15(5), P. 1787 - 1821

Published: Jan. 2, 2025

Lactate is an indispensable substance in various cellular physiological functions and plays regulatory roles different aspects of energy metabolism signal transduction. Lactylation (Kla), a key pathway through which lactate exerts its functions, has been identified as novel posttranslational modification (PTM). Research indicates that Kla essential balancing mechanism variety organisms involved many biological processes pathways. closely related to disease development represents potential important new drug target. In line with existing reports, we searched for newly discovered sites on histone nonhistone proteins; reviewed the mechanisms (particularly focusing enzymes directly reversible regulation Kla, including "writers" (modifying enzymes), "readers" (modification-binding "erasers" (demodifying enzymes); summarized crosstalk between PTMs help researchers better understand widespread distribution diverse functions. Furthermore, considering "double-edged sword" role both pathological contexts, this review highlights "beneficial" states (energy metabolism, inflammatory responses, cell fate determination, development, etc.) "detrimental" pathogenic or inducive effects processes, particularly malignant tumors complex nontumor diseases. We also clarify molecular health disease, discuss feasibility therapeutic Finally, describe detection technologies their applications diagnosis clinical settings, aiming provide insights treatment diseases accelerate translation from laboratory research practice.

Language: Английский

Citations

2
Lactylation in cancer progression and drug resistance DOI
Yuxiu Sun, He Wang,

Zhe Cui

et al.

Drug Resistance Updates, Journal Year: 2025, Volume and Issue: unknown, P. 101248 - 101248

Published: April 1, 2025

Language: Английский

Citations

0
The lactylation modification of proteins plays a critical role in tumor progression DOI Creative Commons

Dai Yi,

Ke Zhou,

Yu Pan

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: March 19, 2025

Lactylation modifications have been shown to be a novel type of protein post-translational (PTMs), providing new perspective for understanding the interaction between cellular metabolic reprogramming and epigenetic regulation. Studies that lactylation plays an important role in occurrence, development, angiogenesis, invasion metastasis tumors. It can not only regulate phenotypic expression functional polarization immune cells, but also participate formation tumor drug resistance through variety molecular mechanisms. In this review, we review latest research progress modification tumors, focusing on its mechanism action cell regulation microenvironment (TME), resistance, aiming provide theoretical basis ideas discovery therapeutic targets methods. Through in-depth analysis modification, it is expected open up direction treatment potential strategies overcoming improving clinical efficacy.

Language: Английский

Citations

0
Lactate metabolism and lactylation in breast cancer: mechanisms and implications DOI Creative Commons

Yifan Qiao,

Yijia Liu,

Ran Ran

et al.

Cancer and Metastasis Reviews, Journal Year: 2025, Volume and Issue: 44(2)

Published: April 28, 2025

Language: Английский

Citations

0
Rewired glycolysis by DTL accelerates oncometabolite L-lactate generation to promote breast cancer progression DOI Creative Commons
Yuhao Liu, Jinting Li, Yiren Cao

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: May 5, 2025

Breast cancer (BC) has become the leading cause of global incidence. Despite therapeutic advances, a critical unmet need persists for identifying novel targets. Our integrated bioinformatics analysis identified DTL, component Cullin-RING ligase (CRL) E3 ubiquitin family, as significantly upregulated in BC tissues. This upregulation correlated with poor patient prognosis, stemness, and metabolic reprogramming, which was driven by genetic alterations such gene amplification reduced promoter methylation. Functional studies demonstrated that DTL promoted breast cell proliferation migration vitro through glycolysis remodeling. Mechanistically, positively regulated key glycolytic enzymes (HK2, ENO1, PKM2, LDHA) independently its canonical activity directly interacted LDHA. Notably, exogenous L-lactate enhanced tumor growth metastasis. Collectively, our findings reveal non-canonical mechanism whereby drives to generate oncometabolite L-lactate, sustains malignancy independent protein degradation. The strong association between adverse clinical outcomes, coupled multifaceted regulatory roles biology, highlighting potential target BC.

Language: Английский

Citations

0