New prognostic features and personalized treatment strategies of mitochondrial related genes in colorectal cancer patients DOI Creative Commons
Qiaobing Xu, Zhiwen Wang,

S.Q. Huang

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 1, 2025

Colorectal cancer (CRC) is a common and aggressive malignancy with the complex varied molecular landscape. Mitochondria play pivotal role in metabolic reprogramming of cells, their function can profoundly influence tumor progression. Therefore, identifying mitochondrial genes immune-related features may offer promising new approach for prognosis CRC. Mitochondrial-associated were retrieved from MITOCARTA 3.0 dataset. The LASSO regression method was applied to identify prognostic genes, while area under ROC curve nomograms used assess robustness model. Single-sample genomic enrichment analysis (ssGSEA) utilized explore relationship between model immune infiltration, drug sensitivity conducted potential therapeutic agents. Cellular assays performed validate effectiveness identified drugs. Key including SUCLG2, ACACB, OSBPL1A, TRAP1, have been as significant markers expression ACACB OSBPL1A progressively increased, SUCLG2 TRAP1 decreased patients. TCGA dataset showed an (AUC) greater than 0.6 1-, 2-, 3-year survival predictions, demonstrating strong this Additionally, strongly correlated particularly CD8 + T checkpoint regulators. Molecular docking revealed that binds dabrafenib at glycine position 747. confirmed effectively inhibited CRC cell migration proliferation, providing avenue. Our findings suggested four mitochondrial-related study provide accurate predictions

Language: Английский

VEGF signaling: Role in angiogenesis and beyond DOI
Pallab Shaw, Shailendra Kumar Dhar Dwivedi, Resham Bhattacharya

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(2), P. 189079 - 189079

Published: Jan. 26, 2024

Language: Английский

Citations

55
An amplification mechanism for weak ELF magnetic fields quantum-bio effects in cancer cells DOI Creative Commons

Amirali Zandieh,

Seyed Peyman Shariatpanahi,

Amir Abas Ravassipour

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 23, 2025

Language: Английский

Citations

2
SLC5A3 depletion promotes apoptosis by inducing mitochondrial dysfunction and mitophagy in gemcitabine-resistant pancreatic cancer cells DOI Creative Commons
Minsoo Kim,

Woosol Chris Hong,

Hyeon Woong Kang

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 7, 2025

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor prognosis, largely due to the rapid development of chemoresistance in patients. Mitochondrial dynamics play crucial role cell survival. Currently, specific mechanisms underlying gemcitabine resistance PDAC remain unknown. In this study, we identified sodium/myo-inositol co-transporter solute carrier family 5 member 3 (SLC5A3) as key modulator promoting PDAC. SLC5A3 levels were significantly upregulated gemcitabine-resistant cells, enhancing their survival by stabilizing mitochondrial functions and inhibiting apoptosis. analysis showed that inhibition disrupted dynamics, leading increased reactive oxygen species production, fission, impaired oxidative phosphorylation. Moreover, activated PTEN-induced kinase 1/Parkin-mediated mitophagy pathway, resulting excessive removal damaged healthy mitochondria, thereby depleting reserves sensitizing cells vivo studies revealed targeting enhanced efficacy reduced tumor growth. Collectively, these results suggest SLC5A3-mediated regulation promising therapeutic strategy overcome

Language: Английский

Citations

2
Cellular senescence and metabolic reprogramming: Unraveling the intricate crosstalk in the immunosuppressive tumor microenvironment DOI Creative Commons
Fusheng Zhang,

Junchen Guo,

Shengmiao Yu

et al.

Cancer Communications, Journal Year: 2024, Volume and Issue: 44(9), P. 929 - 966

Published: July 12, 2024

Abstract The intrinsic oncogenic mechanisms and properties of the tumor microenvironment (TME) have been extensively investigated. Primary features TME include metabolic reprogramming, hypoxia, chronic inflammation, immunosuppression. Previous studies suggest that senescence‐associated secretory phenotypes mediate intercellular information exchange play a role in dynamic evolution TME. Specifically, hypoxic adaptation, dysregulation, phenotypic shifts immune cells regulated by cellular senescence synergistically contribute to development an immunosuppressive thereby promoting progression events. This review provides comprehensive summary processes which regulates tumor‐adapted TME, with focus on complex underlying relationship between changes biological functions cells. available findings components collectively potential applications challenges targeted senescence‐based combination therapies clinical settings are further discussed within context advancing senescence‐related research.

Language: Английский

Citations

12
Mitochondria-Selective Dicationic Small-Molecule Ligand Targeting G-Quadruplex Structures for Human Colorectal Cancer Therapy DOI
Bo‐Xin Zheng,

Wei Long,

Wende Zheng

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(8), P. 6292 - 6312

Published: April 16, 2024

Mitochondria are important drug targets for anticancer and other disease therapies. Certain human mitochondrial DNA sequences capable of forming G-quadruplex structures (G4s) emerging small molecules. Despite some mitochondria-selective ligands being reported delivery against cancers, the ligand design is mostly limited to triphenylphosphonium scaffold. The designed with lipophilic small-sized scaffolds bearing multipositive charges targeting unique feature high membrane potential (MMP) lacking most not G4-targeting. Herein, we report a new dicationic target MMP G4s enhance anticancer. showed marked alteration gene expression substantial induction ROS production, dysfunction, damage, cellular senescence, apoptosis. also exhibited activity HCT116 cancer cells (IC50, 3.4 μM) antitumor efficacy in tumor xenograft mouse model (∼70% weight reduction).

Language: Английский

Citations

10
Accelerated Aging in Cancer Survivors: Cellular Senescence, Frailty, and Possible Opportunities for Interventions DOI Open Access
Shuo Wang, Najla El Jurdi, Bharat Thyagarajan

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3319 - 3319

Published: March 14, 2024

The population of cancer survivors has markedly increased due to the rapid improvements in treatment. However, experience accelerated aging, which leads chronic diseases and other age-related conditions, such as frailty. Those conditions may persist years after diagnosis Cellular senescence, a hallmark is one mechanisms that contribute aging survivors. Several measures, including measures based on clinical markers biomarkers, have been proposed estimate process, some them shown associations with mortality frailty anti-aging interventions, lifestyle changes drugs, proposed. Future research, particularly large-scale studies, needed determine efficiency these interventions before considering their application clinics. This review focuses cellular senescence survivors, assessment process using high prevalence population, well possible opportunities for interventions. A deeper understanding will development effective strategies mitigate improve quality life.

Language: Английский

Citations

9
Hypoxia promotes histone H3K9 lactylation to enhance LAMC2 transcription in esophageal squamous cell carcinoma DOI Creative Commons
Yong Zang, Yu Wang, Jianji Zhang

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(7), P. 110188 - 110188

Published: June 5, 2024

Language: Английский

Citations

9
Metabolic interplays between the tumour and the host shape the tumour macroenvironment DOI
Patricia Altea‐Manzano, Amanda R. Decker-Farrell, Tobias Janowitz

et al.

Nature reviews. Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Language: Английский

Citations

1
Illuminating the immunological landscape: mitochondrial gene defects in pancreatic cancer through a multiomics lens DOI Creative Commons
Hao Chi,

Lanqian Su,

Yalan Yan

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 6, 2024

This comprehensive review delves into the complex interplay between mitochondrial gene defects and pancreatic cancer pathogenesis through a multiomics approach. By amalgamating data from genomic, transcriptomic, proteomic, metabolomic studies, we dissected mechanisms by which genetic variations dictate progression. Emphasis has been placed on roles of these genes in altering cellular metabolic processes, signal transduction pathways, immune system interactions. We further explored how findings could refine therapeutic interventions, with particular focus precision medicine applications. analysis not only fills pivotal knowledge gaps about anomalies but also paves way for future investigations personalized therapy options. finding underscores crucial nexus genetics oncological immunology, opening new avenues targeted treatment strategies.

Language: Английский

Citations

6
Chromosomal 3q amplicon encodes essential regulators of secretory vesicles that drive secretory addiction in cancer DOI Creative Commons
Xiaochao Tan,

Shike Wang,

Guan-Yu Xiao

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(12)

Published: April 25, 2024

Cancer cells exhibit heightened secretory states that drive tumor progression. Here, we identify a chromosome 3q amplicon serves as platform for regulation in cancer. The encodes multiple Golgi-resident proteins, including the scaffold Golgi integral membrane protein 4 (GOLIM4) and ion channel ATPase Secretory Pathway Ca2+ Transporting 1 (ATP2C1). We show GOLIM4 recruits ATP2C1 phosphoprotein 3 (GOLPH3) to coordinate calcium-dependent cargo loading bending vesicle scission. depletion disrupts complex, resulting blockade inhibits progression of 3q-amplified malignancies. In addition its role scaffold, maintains intracellular manganese (Mn) homeostasis by binding excess Mn lumen, which initiates routing Mn-bound lysosomes degradation. treatment types malignancies degrading GOLIM4, interrupts pro-survival autocrine loops attenuates pro-metastatic processes microenvironment. Potentially underlying selective activity against malignancies, co-amplification increases influx into more rapid degradation GOLIM4. These findings functional cooperativity between co-amplified genes underlies secretion targetable addiction

Language: Английский

Citations

4