Mitochondrial ubiquinol oxidation is necessary for tumour growth

Nature, Journal Year: 2020, Volume and Issue: 585(7824), P. 288 - 292

Published: July 8, 2020

Language: Английский

---

Folding the Mitochondrial UPR into the Integrated Stress Response

Trends in Cell Biology, Journal Year: 2020, Volume and Issue: 30(6), P. 428 - 439

Published: April 2, 2020

Language: Английский

---

Tumor glycolysis, an essential sweet tooth of tumor cells

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 86, P. 1216 - 1230

Published: Oct. 28, 2022

Language: Английский

---

Metabolic Reprogramming of Cancer Cells during Tumor Progression and Metastasis

Metabolites, Journal Year: 2021, Volume and Issue: 11(1), P. 28 - 28

Published: Jan. 2, 2021

Cancer cells face various metabolic challenges during tumor progression, including growth in the nutrient-altered and oxygen-deficient microenvironment of primary site, intravasation into vessels where anchorage-independent is required, colonization distant organs environment distinct from that site. Thus, cancer must reprogram their state every step progression. Metabolic reprogramming now recognized as a hallmark supports growth. Elucidating underlying mechanisms may help identifying targets treatment strategies. This review summarizes our current understanding progression metastasis, cell adaptation to microenvironment, defense against oxidative stress vessels, metastasis.

Language: Английский

---

Constructing a novel mitochondrial-related gene signature for evaluating the tumor immune microenvironment and predicting survival in stomach adenocarcinoma

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: March 13, 2023

Abstract Background The incidence and mortality of gastric cancer ranks fifth fourth worldwide among all malignancies, respectively. Accumulating evidences have revealed the close relationship between mitochondrial dysfunction initiation progression stomach cancer. However, rare prognostic models for mitochondrial-related gene risk been built up in Methods In current study, expression value genes adenocarcinoma (STAD) patients were systematically analyzed to establish a model based on available TCGA GEO databases. tumor microenvironment (TME), immune cell infiltration, mutation burden, drug sensitivity also investigated using R language, GraphPad Prism 8 online Results We established including NOX4, ALDH3A2, FKBP10 MAOA validated its predictive power. This indicated that infiltration high-risk group was significantly different from low-risk group. Besides, score closely related TME signature checkpoint molecules, suggesting immunosuppressive might lead poor prognosis groups. Moreover, TIDE analysis demonstrated combined score, or stromal microsatellite status could more effectively predict benefit immunotherapy STAD with stratifications. Finally, rapamycin, PD-0325901 dasatinib found be effective group, whereas AZD7762, CEP-701 methotrexate predicted Conclusions Our results suggest reliable biomarker personalized treatment patients.

Language: Английский

---

Mitochondrial Localized In Situ Self‐Assembly Reprogramming Tumor Immune and Metabolic Microenvironment for Enhanced Cancer Therapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(15)

Published: Jan. 8, 2024

Abstract The inherent immune and metabolic tumor microenvironment (TME) of most solid tumors adversely affect the antitumor efficacy various treatments, which is an urgent issue to be solved in clinical cancer therapy. In this study, a mitochondrial localized situ self‐assembly system constructed remodel TME by improving immunogenicity disrupting plasticity cells. peptide‐based drug delivery can pre‐assembled into nanomicelles vitro form functional nanofibers on mitochondria through cascade‐responsive process involving reductive release, targeted enrichment, self‐assembly. organelle‐specific self‐assemblyeffectively switches role mitophagy from pro‐survival pro‐death, finally induces intense endoplasmic reticulum stress atypical type II immunogenic cell death. Disintegration ultrastructure also impedes cells, greatly promotes immunosuppresive remodeling immunostimulatory TME. Ultimately, effectively suppresses metastases, converts cold hot with enhanced sensitivity radiotherapy checkpoint blockade This study offers universal strategy for spatiotemporally controlling supramolecular sub‐organelles determine fate enhance

Language: Английский

---

Mitocans Revisited: Mitochondrial Targeting as Efficient Anti-Cancer Therapy

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(21), P. 7941 - 7941

Published: Oct. 26, 2020

Mitochondria are essential cellular organelles, controlling multiple signalling pathways critical for cell survival and death. Increasing evidence suggests that mitochondrial metabolism functions indispensable in tumorigenesis cancer progression, rendering mitochondria as plausible targets anti-cancer therapeutics. In this review, we summarised the major strategies of selective targeting their to combat cancer, including metabolism, electron transport chain tricarboxylic acid cycle, redox pathways, ROS homeostasis. We highlight delivering drugs into exhibits enormous potential future therapeutic strategies, with a great advantage potentially overcoming drug resistance. Mitocans, exemplified by mitochondrially targeted vitamin E succinate tamoxifen (MitoTam), selectively target efficiently kill types cells disrupting function, MitoTam currently undergoing clinical trial.

Language: Английский

---

Targeting mitochondria as an anticancer strategy

Cancer Communications, Journal Year: 2019, Volume and Issue: 39(1), P. 1 - 3

Published: Oct. 25, 2019

Mitochondria are organelles controlling adenosine triphosphate (ATP) generation, redox homeostasis, metabolic signaling, and apoptotic pathways. Although glycolysis was traditionally considered as the major source of energy in cancer cells, in-line with so-called “Warburg effect”, mitochondria have been recognized to play a key role oncogenesis [1]. Cancer cells uniquely reprogram their cellular activities support rapid proliferation migration, well counteract genotoxic stress during progression [2]. Further, can switch phenotypes meet challenges high demand macromolecular synthesis [3]. Thus, ability flexibly switching between oxidative phosphorylation (OXPHOS) for survival. The electron transport chain (ETC) function is pivotal mitochondrial respiration, which also needed dihydroorotate dehydrogenase (DHODH) activity that essential de novo pyrimidine [4]. Recent researches demonstrated devoid DNA (mtDNA) lack tumorigenic potential, they re-gain this by acquiring healthy mtDNA from host stromal via horizontal transfer whole [5, 6] recovery respiratory function. Functionally, respiration propels DHODH biosynthesis [7]. Therefore, targeting holds great potential anticancer strategy therapeutic opportunities. Multiple strategies developed target therapies including agents OXPHOS function, glycolysis, tricarboxylic acid (TCA) cycle, pathways, reactive oxygen species (ROS) permeability transition pore complex, DHODH-linked [8, 9]. In research highlights, we demonstrate some most relevant targets therapy. Functional ETC supports generation tumorigenesis. Many inhibitors, such metformin, tamoxifen, α-tocopheryl succinate (α-TOS) 3-bromopyruvate (3BP), act disrupting complexes inducing levels ROS kill A novel approach selective tagging cationic triphenylphosphonium (TPP+) group compounds (e.g., α-TOS, tamoxifen metformin) mitochondrial-targeted therapy, delivering drugs preferentially into cell based on higher transmembrane trigger mitochondria-dependent apoptosis [9, 10]. Both MitoVES (mitochondrially targeted vitamin E complex II) MitoTAM I) prepared TPP+ parental efficiently kills colorectal, lung breast inhibits tumor growth interfering I-/complex II-dependent without systemic toxicity [11, 12]. pathway directly affects providing intermediates, pyruvate, metabolism. Moreover, malignant appears multiple modes resistance oncogenic inhibition [1, 8]. both hold promise an ideal approach. Mitochondria-targeted therapeutics combination glycolytic inhibitors synergistically suppress [9]. Hexokinase II (HKII) isoform enzyme overexpressed plays important maintaining activity. It binds voltage-dependent anion channel (VDAC) outer membrane. As such, HKII will not only inhibit but suppresses anti-apoptotic effects HKII–VDAC interaction. Several hexokinase found growth. FV-429 synthetic flavone potent induce suppression impairing interaction, leading activation mitochondrial-mediated apoptosis. Metformin, drug commonly used treat diabetes, types cancers [13, 14]. report showed metformin carcinoma decrease glucose uptake phosphorylation. Combining 2-deoxyglucose (2-DG), inhibitor, depleted ATP synergistic manner strong synergy combined effect pancreatic cells. mitochondria-targeted drug, carboxy-proxyl (Mito-CP) 2-DG led significant regression, suggesting dual bioenergetic metabolism may offer promising chemotherapeutic [15]. TCA cycle electrons feed drive electrochemical proton gradient required generation. Isocitrate dehydrogenases 1 2 (IDH1, IDH2) catalyzes conversion isocitrate α- ketoglutarate, playing critical tumorigenesis Mutations IDH1 IDH2 different human [16] render them Inhibitors IDHs AGI-5198, AGI-6780, AG-120, AG-221, 3BP, dichloroacetate possess broad range 17]. Bcl-2, Bcl-xL, Bax, Bak intrinsic pathway. Venetoclax, currently approved use patients chronic lymphocytic leukemia [18], navitoclax, TW-37, GX15-070 BM-1197, Bcl-2 or Bcl-xL [8]. Compounds Gossypol, Navitoclax, ABT-737 α-TOS mimetics homology-3 domains through post-mitochondrial signaling [17]. Electron site production, level released due interference ECT cause damage. Oxymatrine reported melanoma generating ROS. Capsaicin, casticin, myricetin display increasing disruption Promoting production death enhance chemotherapy By coupling triphenylamine (TPA) fluorophore BODIPY, fluorescent probe BODIPY-TPA shown gastric balance accumulation [19]. summary, survival Mitochondrial Targeting presents new concept effective therapeutics. Not applicable. LD wrote manuscript. authors read final declare no competing interests.

Language: Английский

---

Glycerol-3-phosphate biosynthesis regenerates cytosolic NAD+ to alleviate mitochondrial disease

Cell Metabolism, Journal Year: 2021, Volume and Issue: 33(10), P. 1974 - 1987.e9

Published: July 15, 2021

Language: Английский

---

Smart transformable nanomedicines for cancer therapy

Biomaterials, Journal Year: 2021, Volume and Issue: 271, P. 120737 - 120737

Published: March 2, 2021

Language: Английский

---