Mitochondrion, Год журнала: 2024, Номер unknown, С. 102003 - 102003
Опубликована: Дек. 1, 2024
Язык: Английский
Nature Communications, Год журнала: 2025, Номер 16(1)
Опубликована: Янв. 2, 2025
Abstract Glucose deprivation, a hallmark of the tumor microenvironment, compels cells to seek alternative energy sources for survival and growth. Here, we show that glucose deprivation upregulates expression mitochondrial-cytochrome c oxidase II (MT-CO2), subunit essential respiratory chain complex IV, in facilitating glutaminolysis sustaining cell survival. Mechanistically, activates Ras signaling enhance MT-CO2 transcription inhibits IGF2BP3, an RNA-binding protein, stabilize mRNA. Elevated increases flavin adenosine dinucleotide (FAD) levels activating lysine-specific demethylase 1 (LSD1) epigenetically upregulate JUN transcription, consequently promoting glutaminase-1 (GLS1) Furthermore, is indispensable oncogenic Ras-induced growth, elevated associated with poor prognosis lung cancer patients. Together, these findings reveal role adapting metabolic stress highlight as putative therapeutic target Ras-driven cancers.
Язык: Английский
Процитировано
3
Nature Cancer, Год журнала: 2025, Номер unknown
Опубликована: Янв. 17, 2025
Язык: Английский
Процитировано
1
Cell Reports Medicine, Год журнала: 2025, Номер unknown, С. 101941 - 101941
Опубликована: Фев. 1, 2025
Highlights•Biguanides activate or suppress TNBC progression in a dose-dependent manner•Biguanides regulate c-Src by the antithetical regulation of AMPK-FAO•Combination dasatinib with metformin suppresses and metastasisSummaryThe biguanide attenuates mitochondrial oxidation is proposed as an anti-cancer therapy. However, recent clinical studies suggest increased proliferation fatty acid β-oxidation (FAO) subgroup patients breast cancer (BC) after Considering that FAO can Src kinase aggressive triple-negative BC (TNBC), we postulate low-dose biguanide-driven AMPK-ACC-FAO signaling may pathway TNBC. The low bioavailability xenografts mimics metformin's vitro effect. Pharmacological genetic inhibition significantly enhances anti-tumor properties biguanides. Lower doses biguanides induce higher signaling. Dasatinib synergistically inhibit patient-derived xenograft growth, but not high-fat diet-fed mice. This combination also metastatic progression. A inhibitors provides synergy to target suffering limited treatment options.Graphical abstract
Язык: Английский
Процитировано
1
Cellular Signalling, Год журнала: 2024, Номер 122, С. 111329 - 111329
Опубликована: Авг. 5, 2024
Язык: Английский
Процитировано
7
Cell Reports, Год журнала: 2025, Номер 44(1), С. 115154 - 115154
Опубликована: Янв. 1, 2025
Recent research has shown that mtDNA-deficient cancer cells (ρ0 cells) acquire mitochondria from tumor stromal to restore respiration, facilitating formation. We investigated the role of Miro1, an adaptor protein involved in movement along microtubules, this phenomenon. Inducible Miro1 knockout (Miro1KO) mice markedly delayed formation after grafting ρ0 cells. Miro1KO with fluorescently labeled revealed delay was due hindered mitochondrial transfer grafted B16 cells, which impeded recovery respiration and growth. led perinuclear accumulation impaired mobility network. In vitro experiments decreased association compromising via tunneling nanotubes (TNTs) mesenchymal Here we show horizontal mouse melanoma models vivo its involvement TNTs.
Язык: Английский
Процитировано
0
Redox Biology, Год журнала: 2025, Номер 81, С. 103536 - 103536
Опубликована: Фев. 10, 2025
Язык: Английский
Процитировано
0
Science Advances, Год журнала: 2025, Номер 11(15)
Опубликована: Апрель 9, 2025
OxPhos inhibitors have struggled to show a clinical benefit because of their inability distinguish healthy from cancerous mitochondria. Herein, we describe an actionable bioenergetic mechanism unique acute myeloid leukemia (AML) Unlike cells that couple respiration ATP synthesis, AML mitochondria support inner-membrane polarization by consuming ATP. Matrix consumption allows survive stress. Thus, hypothesized may resist chemotherapy-induced cell death reversing the synthase reaction. In support, BCL-2 inhibition with venetoclax abolished flux without affecting mitochondrial polarization. surviving cells, sustained depended on matrix consumption. Mitochondrial was further enhanced in made refractory venetoclax, consequential down-regulations endogenous F 1 -ATPase inhibitor ATP5IF1. Knockdown ATP5IF1 conferred resistance, while overexpression impaired activity and heightened sensitivity venetoclax. These data identify as cancer cell–intrinsic vulnerability context targeted chemotherapy.
Язык: Английский
Процитировано
0
Metabolites, Год журнала: 2024, Номер 14(6), С. 318 - 318
Опубликована: Май 31, 2024
Metabolic reprogramming is a hallmark of cancer, driving the development therapies targeting cancer metabolism. Stable isotope tracing has emerged as widely adopted tool for monitoring metabolism both in vitro and vivo. Advances instrumentation new tracers, metabolite databases, data analysis tools have expanded scope studies across these scales. In this review, we explore latest advancements metabolic analysis, spanning from experimental design stable isotope-labeling metabolomics to sophisticated techniques. We highlight successful applications research, particularly focusing on ongoing clinical trials utilizing characterize disease progression, treatment responses, potential mechanisms resistance anticancer therapies. Furthermore, outline key challenges discuss strategies address them, aiming enhance our understanding biochemical basis
Язык: Английский
Процитировано
2
Cancer Treatment Reviews, Год журнала: 2024, Номер 129, С. 102802 - 102802
Опубликована: Июль 11, 2024
Immune checkpoint inhibition has transformed the treatment landscape of advanced melanoma and long-term survival patients is now possible. However, at least half do not benefit sufficiently. Metabolic reprogramming a hallmark cancer cells may contribute to both tumour growth immune evasion by tumour. Preclinical studies have indeed demonstrated that modulating metabolism can reduce while improving functionality cells. Since metabolic pathways are commonly shared between cells, it essential understand how in influences intricate balance pro-and anti-tumour effects microenvironment. The key question whether inhibit cell as well facilitate an response. Here, we review current knowledge on effect response melanoma. We summarise non-cancerous microenvironment discuss models techniques available study metabolic-immune interaction. Finally, clinical use these improve our understanding interventions tip towards favourable, permissive patients.
Язык: Английский
Процитировано
2
Lipids in Health and Disease, Год журнала: 2024, Номер 23(1)
Опубликована: Ноя. 14, 2024
Pancreatic neoplasm, a highly aggressive and often fatal cancer, poses challenges due to late detection nonspecific symptoms. Therefore, both early diagnosis appropriate therapeutic approaches are necessary augment the condition of these patients. Cancer cells undergo metabolic deregulation, which enables their proliferation, survival, invasion. As result, it is crucial focus on pathways in prevalent cancers explore treatment strategies that target control tumor growth effectively. This particularly relevant like pancreatic numerous alterations. The ketogenic regimen, characterized by low carbohydrate protein contents high-fat sources, does not involve caloric restriction. allows for induction ketogenesis an increase ketone bodies, while insulin glucose levels remain even after meals. unique state may influence microenvironment. Given lack unanimous agreement precise role mechanism diet, this review aims clarify diagnostic value accuracy bodies various types tumors potential anti-cancer effects diet when used alone or conjunction with chemotherapy, also determine be as adjuvant therapy. outcomes study instrumental enhancing our understanding benefits drawbacks associated employing management cancer.
Язык: Английский
Процитировано
2