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

Pilot Study: Initial Investigation Suggests Differences in EMT-Associated Gene Expression in Breast Tumor Regions DOI Creative Commons
Kylie L. King, Hamed Abdollahi, Zoë Dinkel

et al.

Computational and Structural Biotechnology Journal, Journal Year: 2025, Volume and Issue: 27, P. 548 - 555

Published: Jan. 1, 2025

Language: Английский

Citations

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DNA Methylation and Demethylation in Triple-Negative Breast Cancer: Associations with Clinicopathological Characteristics and the Chemotherapy Response DOI Creative Commons
Kateryna Tarhonska, Mateusz Wichtowski, Thomas Wow

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 585 - 585

Published: Feb. 26, 2025

Objectives: Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options due to the absence of estrogen, progesterone receptors, and HER2 expression. This study examined impact DNA methylation demethylation markers in tumor tissues on TNBC patients’ response neoadjuvant chemotherapy (NACT) analyzed correlation between 5-methylcytosine (5-mC) 5-hydroxymethylcytosine (5-hmC) clinicopathological characteristics, offering new insights into predictive value these epigenetic markers. Methods: The included 53 female patients, 19 whom received before surgery. Global levels were quantified using ELISA-based method measure 5-mC 5-hmC content isolated from pre-treatment biopsy samples (in patients undergoing NACT) postoperative without NACT). Results: In who NACT, those disease progression had significantly higher pretreatment (p = 0.028) a trend toward 0.054) compared pathological complete response, partial or stable disease. Higher associated grade 0.039 p 0.017, respectively). Additionally, positive was observed Ki-67 proliferation marker both (rS 0.340, 0.049) 0.341, 0.048) tissues. Conclusions: Our highlights potential global as predictors aggressiveness TNBC. Further research larger cohorts necessary validate markers’ prognostic value.

Language: Английский

Citations

0
The role of Prolyl 3-Hydroxylase 1 (P3H1) in tumor development and prognosis: a pan-cancer analysis with validation in colonic adenocarcinoma DOI
Yanqin Chen, Moazzam Ali, Muhammad Tayyab

et al.

American Journal of Translational Research, Journal Year: 2025, Volume and Issue: 17(2), P. 770 - 790

Published: Jan. 1, 2025

Cancer is a multifaceted disease characterized by unregulated cell proliferation, evasion of apoptosis, and metastasis. Recent studies have highlighted the importance extracellular matrix remodeling post-translational modifications in tumorigenesis. Prolyl 3-hydroxylase 1 (P3H1), an enzyme involved collagen hydroxylation, has gained attention for its role cancer progression. This study investigates P3H1 expression, prognostic value, functional relevance across multiple human cancers using combination bioinformatic experimental approaches. Using The Genome Atlas (TCGA) data from TIMER2.0 UALCAN databases, we observed significant upregulation mRNA protein various cancers. Prognostic analysis GEPIA2 KM plotter revealed that high expression correlates with poorer overall survival colon adenocarcinoma (COAD), kidney renal clear carcinoma (KIRC), liver hepatocellular (LIHC). Further, genetic promoter methylation analyses showed low mutation frequencies reduced specific types. Functional pathway enrichment indicated formation, endoplasmic reticulum activity, pathways such as ECM-receptor interaction PI3K-Akt signaling. Validation linked immunosorbent assay COAD patient serum samples demonstrated significantly elevated levels compared to healthy controls, AUC approaching 1.0 receiver operating characteristic (ROC) curve analysis. suggests potential diagnostic biomarker. Additionally, experiments were conducted cells assess P3H1's Knockdown HCT116 resulted reduction colony migratory abilities these cells. These findings emphasize COAD, KIRC, LIHC pathogenesis possible utility clinical diagnosis.

Language: Английский

Citations

0
Extracellular vesicles in triple-negative breast cancer: current updates, challenges and future prospects DOI Creative Commons
Prashant Tiwari, Anis Ahmad Chaudhary, Saurabh Gupta

et al.

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 12

Published: April 14, 2025

Breast cancer (BC) remains a complex and widespread problem, affecting millions of women worldwide, Among the various subtypes BC, triple-negative breast (TNBC) is particularly challenging, representing approximately 20% all BC cases, survival rate TNBC patients generally worse than other BC. heterogeneous disease characterized by lack expression three receptors: estrogen (ER), progesterone (PR), human epidermal growth factor receptor 2 (HER2), resulting conventional hormonal therapies are ineffective for its management. Despite therapeutic approaches have been explored, but no definitive solution has found yet TNBC. Current treatments options chemotherapy, immunotherapy, radiotherapy surgery, although, these some limitations, such as development resistance to anti-cancer drugs, off-target toxicity, which remain primary obstacles significant challenges Several findings shown that EVs exhibit promise in many diseases, similar important role observed types tumor. Studies suggest may offer potential management This review highlights multifaceted roles TNBC, emphasizing their involvement progression, diagnosis approach, well biomarkers drug delivery.

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