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

RNA methyltransferase METTL16: from molecular mechanisms to therapeutic prospects in cancers DOI

Zhuozheng Shi,

Xiankui Cao,

Yiming Ma

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217698 - 217698

Published: April 1, 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