The mitochondria as an emerging target of self-renewal in T-cell acute lymphoblastic leukemia DOI Creative Commons

Majd A. Al-Hamaly,

Evelyn Winter,

Jessica S. Blackburn

и другие.

Cancer Biology & Therapy, Год журнала: 2025, Номер 26(1)

Опубликована: Фев. 4, 2025

Acute lymphocytic leukemia (ALL) is the most common in children, with T-cell subtype (T-ALL) accounting for 15% of those cases. Despite advancements treatment T-ALL, patients still face a dismal prognosis following their first relapse. Relapse can be attributed to inability chemotherapy agents eradicate stem cells (LSC), which possess self-renewal capabilities and are responsible long-term maintenance disease. Mitochondria have been recognized as therapeutic vulnerability cancer cells, including LSCs. Mitocans shown promise T-ALL both vitro vivo, some currently early-phase clinical trials. However, due challenges studying LSCs our understanding how mitochondrial function influences remains limited. This review highlights emerging literature on targeting mitochondria diverse models, emphasizing specific vulnerabilities linked LSC potential significantly improve treatment.

Язык: Английский

Mitochondrial Metabolism in Carcinogenesis and Cancer Therapy DOI Open Access
Hadia Moindjie,

Sylvie Rodrigues-Ferreira,

Clara Nahmias

и другие.

Cancers, Год журнала: 2021, Номер 13(13), С. 3311 - 3311

Опубликована: Июль 1, 2021

Carcinogenesis is a multi-step process that refers to transformation of normal cell into tumoral neoplastic cell. The mechanisms promote tumor initiation, promotion and progression are varied, complex remain be understood. Studies have highlighted the involvement oncogenic mutations, genomic instability epigenetic alterations as well metabolic reprogramming, in different processes oncogenesis. However, underlying still clarified. Mitochondria central organelles at crossroad various energetic metabolisms. In addition their pivotal roles bioenergetic metabolism, they control redox homeostasis, biosynthesis macromolecules apoptotic signals, all which linked carcinogenesis. present review, we discuss how mitochondria contribute initiation carcinogenesis through gene mutations production oncometabolites, reprogramming mitochondrial dynamics. Finally, metabolism promising target for development novel therapeutic strategies.

Язык: Английский

Процитировано

67
Metabolic tricks of cancer cells DOI
Kateřina Hönigová, Jiří Navrátil, Barbora Peltanová

и другие.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2022, Номер 1877(3), С. 188705 - 188705

Опубликована: Март 8, 2022

Язык: Английский

Процитировано

51
Engine shutdown: migrastatic strategies and prevention of metastases DOI Creative Commons
Martina Raudenská,

Kateřina Petrláková,

Tamara Juriňáková

и другие.

Trends in cancer, Год журнала: 2023, Номер 9(4), С. 293 - 308

Опубликована: Фев. 15, 2023

Most cancer-related deaths among patients with solid tumors are caused by metastases. Migrastatic strategies represent a unique therapeutic approach to prevent all forms of cancer cell migration and invasion. Because the machinery has been shown promote metastatic dissemination, successful migrastatic therapy may reduce need for high-dose cytotoxic therapies that currently used risk dissemination. In this review we focus on anti-invasive antimetastatic hold promise treatment tumors. The best targets would be those required motility, such as ATP availability, mitochondrial metabolism, cytoskeletal dynamics contractility.

Язык: Английский

Процитировано

34
Mitochondria as intracellular signalling organelles. An update DOI Creative Commons
Lucia‐Doina Popov

Cellular Signalling, Год журнала: 2023, Номер 109, С. 110794 - 110794

Опубликована: Июль 6, 2023

Traditionally, mitochondria are known as "the powerhouse of the cell," responsible for energy (ATP) generation (by electron transport chain, oxidative phosphorylation, tricarboxylic acid cycle, and fatty ß-oxidation), regulation several metabolic processes, including redox homeostasis, calcium signalling, cellular apoptosis. The extensive studies conducted in last decades portray multifaceted signalling organelles that ultimately command cells' survival or death. Based on current knowledge, we'll outline mitochondrial to other intracellular compartments homeostasis pathology-related stress conditions here. following topics discussed: (i) mtROS mitohormesis, (ii) Ca2+ signalling; (iii) anterograde (nucleus-to-mitochondria) retrograde (mitochondria-to-nucleus) signal transduction, (iv) mtDNA role immunity inflammation, (v) induction mitophagy- apoptosis - cascades, (vi) dysfunctions (mitochondriopathies) cardiovascular, neurodegenerative, malignant diseases. novel insights into molecular mechanisms mitochondria-mediated can explain adaptation environmental stresses achieve cell survival.

Язык: Английский

Процитировано

28
Mitochondrial DNA-targeted therapy: A novel approach to combat cancer DOI Creative Commons

Yumeng Lin,

Bowen Yang, Yibo Huang

и другие.

Cell Insight, Год журнала: 2023, Номер 2(4), С. 100113 - 100113

Опубликована: Июль 22, 2023

Mitochondrial DNA (mtDNA) encodes proteins and RNAs that are essential for mitochondrial function cellular homeostasis, participates in important processes of bioenergetics metabolism. Alterations mtDNA associated with various diseases, especially cancers, considered as biomarkers some types tumors. Moreover, alterations have been found to affect the proliferation, progression metastasis cancer cells, well their interactions immune system tumor microenvironment (TME). The role development makes it a significant target treatment. In recent years, many novel therapeutic methods targeting emerged. this study, we first discussed how cancerogenesis is triggered by mutations, including gene copy number, aberrant expression epigenetic modifications. Then, described detail mechanisms underlying between extramitochondrial environment, which crucial understanding efficacy safety mtDNA-targeted therapy. Next, provided comprehensive overview progress therapy strategies mtDNA. We classified them into two categories based on action: indirect direct strategies. Indirect aimed induce damage dysfunction modulating pathways involved stability integrity, while utilized molecules can selectively bind or cleave achieve efficacy. This study highlights importance treatment, will provide insights future research targeted drugs

Язык: Английский

Процитировано

22
Mitochondria in biology and medicine – 2023 DOI
B. Disha, Rohan Peter Mathew, Ashwin Dalal

и другие.

Mitochondrion, Год журнала: 2024, Номер 76, С. 101853 - 101853

Опубликована: Фев. 28, 2024

Язык: Английский

Процитировано

8
Targeting mitochondrial ion channels for cancer therapy DOI Creative Commons
Ildikò Szabó, Mario Zoratti, Lucia Biasutto

и другие.

Redox Biology, Год журнала: 2020, Номер 42, С. 101846 - 101846

Опубликована: Дек. 25, 2020

Pharmacological targeting of mitochondrial ion channels is emerging as a promising approach to eliminate cancer cells; most these are differentially expressed and/or regulated in cells comparison healthy ones, this strategy may selectively the former. Perturbation fluxes across outer and inner membranes linked alterations redox state, membrane potential bioenergetic efficiency. This leads indirect modulation oxidative phosphorylation, which is/may be fundamental for both stem cell survival. Furthermore, given crucial contribution mitochondria intrinsic apoptosis, their leading cytochrome c release great advantage case resistance drugs triggering apoptotic events upstream phase. In present review, we give an overview known modulators capable killing cells. addition, discuss state-of-the-art strategies using mitochondriotropic or peptide-based approaches allowing more efficient selective channel-linked events.

Язык: Английский

Процитировано

58
Rocaglamide promotes the infiltration and antitumor immunity of NK cells by activating cGAS-STING signaling in non-small cell lung cancer DOI Creative Commons

Xuewei Yan,

Chao Yao, Fang Cheng

и другие.

International Journal of Biological Sciences, Год журнала: 2021, Номер 18(2), С. 585 - 598

Опубликована: Дек. 15, 2021

Background: Natural killer (NK) cell-based immunotherapy is clinically limited due to insufficient tumor infiltration in solid tumors. We have previously found that the natural product rocaglamide (RocA) can enhance NK cell-mediated killing of non-small cell lung cancer (NSCLC) cells by inhibiting autophagy, and autophagic inhibition has been shown increase melanoma. Therefore, we hypothesized RocA could NSCLC autophagy inhibition. Methods: Flow cytometry, RNA-sequencing, real-time PCR, Western blotting analysis, xenograft model were utilized assess underlying mechanism. Results: significantly increased expressions CCL5 CXCL10 cells, which not be reversed inhibitions autophagy/ULK1, JNK NF-κB. However, such up-regulation suppressed TKB1 STING. Furthermore, dramatically activated cGAS (cyclic GMP-AMP synthase)-STING (stimulator interferon genes) signaling pathway, inhibition/depletion STING ablated CXCL10, infiltration, regression induced RocA. Besides, damaged mitochondrial DNA (mtDNA) promoted cytoplasmic release mtDNA. The mPTP inhibitor cyclosporin A reverse RocA-induced Conclusions: promote activating cGAS-STING via targeting mtDNA, but autophagy. Taken together, our current findings suggested was a potent agonist had promising potential immunotherapy, especially immunotherapy.

Язык: Английский

Процитировано

48
Mitochondrial K+ channels and their implications for disease mechanisms DOI
Vanessa Checchetto, Luigi Leanza, Diego De Stefani

и другие.

Pharmacology & Therapeutics, Год журнала: 2021, Номер 227, С. 107874 - 107874

Опубликована: Апрель 27, 2021

Язык: Английский

Процитировано

45
Intercellular Communication in the Brain through Tunneling Nanotubes DOI Open Access

Khattar E. Khattar,

Janice Safi,

Anne‐Marie Rodriguez

и другие.

Cancers, Год журнала: 2022, Номер 14(5), С. 1207 - 1207

Опубликована: Фев. 25, 2022

Intercellular communication is essential for tissue homeostasis and function. Understanding how cells interact with each other paramount, as crosstalk between often dysregulated in diseases can contribute to their progression. Cells communicate through several modalities, including paracrine secretion specialized structures ensuring physical contact them. Among these intercellular structures, tunneling nanotubes (TNTs) are now recognized a means of cell-to-cell the exchange cellular cargo, controlled by variety biological triggers, described here. fundamental brain It allows dialogue many cells, neurons, astrocytes, oligodendrocytes, glial microglia, necessary proper development function brain. We highlight here role TNTs connecting physiological functioning pathologies such stroke, neurodegenerative diseases, gliomas. processes could pave way future therapies.

Язык: Английский

Процитировано

35