Momordicine-I suppresses head and neck cancer growth by modulating key metabolic pathways DOI Creative Commons
Debojyoty Bandyopadhyay,

Ellen T. Tran,

Rajan Patel

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Dec. 18, 2024

One of the hallmarks cancer is metabolic reprogramming which controls cellular homeostasis and therapy resistance. Here, we investigated effect momordicine-I (M-I), a key bioactive compound from Momordica charantia (bitter melon), on pathways in human head neck (HNC) cells mouse HNC tumorigenicity model. We found that M-I treatment significantly reduced expression glycolytic molecules, SLC2A1 (GLUT-1), HK1, PFKP, PDK3, PKM, LDHA at mRNA protein levels. further observed lactate accumulation, suggesting glycolysis was perturbed treated cells. Metabolomic analyses confirmed marked reduction TCA cycle metabolites M-I-treated downregulated essential enzymes involved de novo lipogenesis, including ACLY, ACC1, FASN, SREBP1, SCD1. Using shotgun lipidomics, significant increase lysophosphatidylcholine phosphatidylcholine loss Subsequently, dysregulation mitochondrial membrane potential oxygen consumption after treatment. induced autophagy, activated AMPK inhibited mTOR Akt signaling leading to apoptosis. However, blocking autophagy did not rescue M-I-mediated alterations an independent mechanism action. MOC2 cell tumors displayed Hk1, Pdk3, Fasn, Acly expression. In conclusion, our study revealed inhibits glycolysis, lipid metabolism, induces reduces tumor volume mice. Therefore, has for important therapeutic implications.

Language: Английский

SMAC-armed oncolytic virotherapy enhances the anticancer activity of PD1 blockade by modulating PANoptosis DOI Creative Commons
Fanghui Chen, Liwei Lang, Jianqiang Yang

et al.

Biomarker Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 9, 2025

Language: Английский

Citations

2
Heat shock proteins as hallmarks of cancer: insights from molecular mechanisms to therapeutic strategies DOI Creative Commons

Wei‐Fang Zuo,

Qiwen Pang, Xinyu Zhu

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Sept. 4, 2024

Language: Английский

Citations

11
Head and neck cancer: pathogenesis and targeted therapy DOI Creative Commons
Yan Liu, Nannan Zhang,

Yi Wen

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(9)

Published: Aug. 21, 2024

Head and neck cancer (HNC) is a highly aggressive type of tumor characterized by delayed diagnosis, recurrence, metastasis, relapse, drug resistance. The occurrence HNC were associated with smoking, alcohol abuse (or both), human papillomavirus infection, complex genetic epigenetic predisposition. Currently, surgery radiotherapy are the standard treatments for most patients early-stage HNC. For recurrent or metastatic (R/M) HNC, first-line treatment platinum-based chemotherapy combined antiepidermal growth factor receptor cetuximab, when resurgery radiation therapy not an option. However, curing remains challenging, especially in cases metastasis. In this review, we summarize pathogenesis including changes, abnormal signaling pathways, immune regulation mechanisms, along all potential therapeutic strategies such as molecular targeted therapy, immunotherapy, gene modifications, combination therapies. Recent preclinical clinical studies that may offer future research on also discussed. Additionally, new targets methods, antibody-drug conjugates, photodynamic radionuclide mRNA vaccines, have shown promising results trials, offering prospects

Language: Английский

Citations

6
Regulation of CD73 on NAD metabolism: Unravelling the interplay between tumour immunity and tumour metabolism DOI Creative Commons

Jianhao Zhan,

Le Huang,

Liyan Niu

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 1, 2024

Abstract CD73, a cell surface-bound nucleotidase, serves as crucial metabolic and immune checkpoint. Several studies have shown that CD73 is widely expressed on cells plays critical role in escape, adhesion migration costimulatory molecule for T factor adenosine production. However, recent revealed the protumour effects of are not limited to merely inhibiting antitumour response. Nicotinamide adenine dinucleotide (NAD+) vital bioactive organisms essential regulatory roles diverse biological processes within tumours. Accumulating evidence has demonstrated involved transport metabolism NAD, thereby regulating tumour promote growth proliferation. This review provides holistic view CD73-regulated NAD + complex network further highlights emerging novel target cancer therapies.

Language: Английский

Citations

5
Hsp90 Promotes Gastric Cancer Cell Metastasis and Stemness by Regulating the Regional Distribution of Glycolysis‐Related Metabolic Enzymes in the Cytoplasm DOI Creative Commons
Shiya Liu,

Gaigai Shen,

Xuanyu Zhou

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: June 14, 2024

Heat-shock protein 90 (Hsp90) plays a crucial role in tumorigenesis and tumor progression; however, its mechanism of action gastric cancer (GC) remains unclear. Here, the Hsp90 GC metabolism is focus this research. High expression tissues can interact with glycolysis, collectively affecting prognosis clinical samples. Both vitro vivo experiments demonstrate that able to regulate migration stemness properties cells. Metabolic phenotype analyses indicate influences glycolytic metabolism. Mechanistically, interacts glycolysis-related enzymes, forming multienzyme complexes enhance glycolysis efficiency yield. Additionally, binds cytoskeleton-related proteins, regulating regional distribution enzymes at cell margin lamellar pseudopods. This effect could lead local increase efficient energy supply from further promoting epithelial-mesenchymal transition (EMT) metastasis. In summary, Hsp90, through interaction metabolic related forms multi-enzyme regulates by dynamic cytoskeletal adjustments, thereby These conclusions also support potential for combined targeted approach involving cytoskeleton therapy.

Language: Английский

Citations

4
HSP90 co-regulates the formation and nuclear distribution of the glycolytic output complex to promote resistance and poor prognosis in gastric cancer patients DOI Creative Commons

Gaigai Shen,

Shiya Liu,

Yuanting Cao

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 10, 2025

Resistance to treatment is a critical factor contributing poor prognosis in gastric cancer patients. HSP90 has emerged as promising therapeutic target; however, its role regulating tumor metabolic pathways, particularly glycolysis, remains poorly understood, which limits clinical application. We identified proteins that directly interact with using immunoprecipitation (IP) followed by mass spectrometry. The relationship between and glycolysis was further investigated through transcriptomic analyses vitro experiments. Mechanistic insights were obtained spectrometry, co-immunoprecipitation (Co-IP) assays, drug sensitivity tests, bioinformatics analyses. Additionally, we developed scoring system based on data evaluate prognostic significance association resistance Our multi-omics studies revealed regulates influences the stemness properties of cells. Mechanistically, facilitates assembly glycolytic multi-enzyme complex, termed HGEO enhances metabolism. formation multienzyme complex comprising key enzymes including PGK1, PKM2, ENO1, LDHA, thereby facilitating production final products. refer this "HSP90-Glycolytic Output Complex" (HGEO Complex). quantified phenomenon (HGScore), finding patients high HGScore exhibited more malignant signatures, increased treatment, poorer prognoses. Furthermore, demonstrated localized nucleus, regulated nuclear lamina protein LMNA, contributes adverse outcomes. In experiments indicated inhibiting sensitizes cells chemotherapy. findings suggest LMNA mediated localization enhancing traits mechanisms cancer. Targeting pathway may offer novel strategy improve

Language: Английский

Citations

0
The regulatory role and mechanism of energy metabolism and immune response in head and neck cancer DOI Creative Commons

Haofan Li,

Peng Qiu,

Linda Oyang

et al.

Genes & Diseases, Journal Year: 2025, Volume and Issue: unknown, P. 101607 - 101607

Published: March 1, 2025

Language: Английский

Citations

0
Exploring the impact of GSTM1 as a novel molecular determinant of survival in head and neck cancer patients of African descent DOI Creative Commons
Fan Yang, Fanghui Chen, Chloe Shay

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: July 23, 2024

Abstract Background Blacks/African American (BAA) patients diagnosed with head and neck squamous cell carcinoma (HNSCC) have worse survival outcomes than White patients. However, the mechanisms underlying racial disparities in HNSCC not been thoroughly characterized. Methods Data on gene expression, copy number variants (CNVs), mutations, methylation were obtained from 6 cancer datasets. Comparative bioinformatics analysis of above genomic features was performed between BAAs Whites. The expression pattern GSTM1 validated by immunohistochemistry using tumor tissue microarray (TMA). Effect knockdown assessed proliferation, colony formation, development an orthotopic mouse model. changes protein kinases determined Proteome Profiler Human Phospho-Kinase Array Kit cells or without knockdown. Results We identified ancestry-related differential profiles HNSCC. Specifically, BAA HNSCC, FAT1 mutations associated its SALL3 correlated CNVs, RTP4 showed inverse correlation methylation. Notably, emerged as a prognostic risk factor for high CNVs levels correlating poor overall Immunohistochemistry results newly developed in-house TMA In model, significantly inhibited malignant progression tumors derived BAAs. contrast, loss did affect originating Mechanistically, suppressed HSP27 phosphorylation β-catenin cells, but cells. This effect at least partially contributes to Conclusion study identifies novel molecular determinant African descent. It also provides basis future research focused identifying determinants developing therapeutic interventions improve

Language: Английский

Citations

1
ETS1 Promotes Aerobic Glycolysis and Growth in Head and Neck Squamous Cell Carcinoma by Targeting RRAS2 DOI
Jianguo Liu, Zhi Wang, Xiaoyan Tian

et al.

Biochemical Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

Language: Английский

Citations

0
Momordicine-I suppresses head and neck cancer growth by modulating key metabolic pathways DOI Creative Commons
Debojyoty Bandyopadhyay,

Ellen T. Tran,

Rajan Patel

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Dec. 18, 2024

One of the hallmarks cancer is metabolic reprogramming which controls cellular homeostasis and therapy resistance. Here, we investigated effect momordicine-I (M-I), a key bioactive compound from Momordica charantia (bitter melon), on pathways in human head neck (HNC) cells mouse HNC tumorigenicity model. We found that M-I treatment significantly reduced expression glycolytic molecules, SLC2A1 (GLUT-1), HK1, PFKP, PDK3, PKM, LDHA at mRNA protein levels. further observed lactate accumulation, suggesting glycolysis was perturbed treated cells. Metabolomic analyses confirmed marked reduction TCA cycle metabolites M-I-treated downregulated essential enzymes involved de novo lipogenesis, including ACLY, ACC1, FASN, SREBP1, SCD1. Using shotgun lipidomics, significant increase lysophosphatidylcholine phosphatidylcholine loss Subsequently, dysregulation mitochondrial membrane potential oxygen consumption after treatment. induced autophagy, activated AMPK inhibited mTOR Akt signaling leading to apoptosis. However, blocking autophagy did not rescue M-I-mediated alterations an independent mechanism action. MOC2 cell tumors displayed Hk1, Pdk3, Fasn, Acly expression. In conclusion, our study revealed inhibits glycolysis, lipid metabolism, induces reduces tumor volume mice. Therefore, has for important therapeutic implications.

Language: Английский

Citations

0