Journal: Journal of Nanobiotechnology
Article Title: Nanomedicine novel strategies: deciphering the EV-metabolic axis as a natural nanocarrier network in lung cancer progression and cachexia
doi: 10.1186/s12951-026-04367-5
Figure Lengend Snippet: EV-mediated metabolic regulatory network in the lung cancer microenvironment. This schematic illustrates the multidimensional regulatory roles of EVs derived from tumor cells, immune cells, and stromal cells in driving the metabolic reprogramming that defines the TME. These EVs function as pivotal intercellular messengers, transferring a heterogeneous cargo of bioactive molecules—including miRNAs, lncRNAs, circRNAs, functional proteins, and metabolites—to recipient cells within the TME. By delivering this molecular cargo, EVs intricately modulate core metabolic pathways essential for tumor survival and progression, such as glycolysis (regulating glucose uptake via GLUT1/GLUT4, HK activity, and lactate secretion through LDHA), lipid metabolism (spanning fatty acid synthesis, β-oxidation, and cholesterol/lipogenesis pathways orchestrated by SREBP and GLS1), and amino acid metabolism (with glutamine utilization via SLC7A5/SLC1A5 and c-Myc-dependent regulation as central nodes). Beyond these core pathways, the figure also delineates EV-mediated regulation of complementary cellular processes: pH homeostasis (via CA and the sodium-hydrogen exchanger NHE1), redox balance (through modulation of the NADPH/NADH ratio by NAMPT and nicotinamide), and autophagy (governed by mTOR, ULK1, and the LKB1-AMPK signaling axis). Visually, the schematic utilizes distinct elements-color-coded molecular categories (e.g., RNA, protein, metabolite), directional arrows denoting regulatory directionality, and annotations for canonical signaling cascades (e.g., Ras-PI3K-AKT, LKB1-AMPK, and c-Myc-driven transcriptional programs)-to clarify the intricate crosstalk between EVs cargo, recipient cell metabolic rewiring, and TME remodeling. Together, this representation highlights how EV-mediated molecular transfer reshapes metabolic networks to sustain tumor growth, evade immune detection, and adapt to the nutrient-deprived, hypoxic conditions of the TME, thereby underscoring the therapeutic potential of targeting EV-driven metabolic crosstalk. GLUT1/4, Glucose Transporter 1/4; HK, Hexokinase; LDHA, Lactate Dehydrogenase A; SREBP, Sterol Regulatory Element-Binding Protein; GLS1, Glutaminase 1; SLC7A5/1A5, Solute Carrier Family 7 Member 5/1 Member 5; c-Myc, Cellular Myelocytomatosis Oncogene; CA, Carbonic Anhydrase; NHE1, Sodium-Hydrogen Exchanger 1; NADPH/NADH, Nicotinamide Adenine Dinucleotide Phosphate/Nicotinamide Adenine Dinucleotide; NAMPT, Nicotinamide Phosphoribosyltransferase; ULK1, Unc-51 Like Autophagy Activating Kinase 1; LKB1-AMPK, Liver Kinase B1-AMP-activated Protein Kinase
Article Snippet: , TKI-resistant LCCs , TKI-sensitive LCCs, NFs, epithelial cells , Exosome isolation kit , EVs/ SLC1A5, SLC25A5 , Enhances glutamine uptake via SLC1A5, activates STAT3 pathway , in vitro and in vivo and clinical study , Induces drug resistance, transforms NFs to CAFs, enhances invasion , [ ] .
Techniques: Derivative Assay, Transferring, Functional Assay, Activity Assay, Binding Assay
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