Complex roles of autophagy in cancer development, immune evasion, and drug resistance

Drug Resistance Updates, Journal Year: 2024, Volume and Issue: 78, P. 101170 - 101170

Published: Nov. 15, 2024

Language: Английский

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MELK prevents radiofrequency ablation-induced immunogenic cell death and antitumor immune response by stabilizing FABP5 in hepatocellular malignancies

Military Medical Research, Journal Year: 2025, Volume and Issue: 12(1)

Published: Jan. 27, 2025

Abstract Background Radiofrequency ablation (RFA) is an efficient treatment with unlimited potential for liver cancer that can effectively reduce patient mortality. Understanding the biological process related RFA important improving strategy. This study aimed to identify critical targets regulating efficacy of RFA. Methods The in hepatocellular carcinoma (HCC) tumor models vivo, was analyzed by RNA sequencing technology. heat vitro HCC cells also constructed explore mechanism after cells. Nanoparticles high affinity were applied as a new therapy interfere expression maternal embryonic leucine zipper kinase (MELK). Results It found upregulated MELK expression, and inhibition promoted immunogenic cell death antitumor response, including anti-tumoral macrophage polarization increased CD8 + T cytotoxicity HCC. Mechanically, binds fatty acid-binding protein 5 (FABP5), affects its ubiquitination through K48R pathway increase stability, thereby activating B (Akt)/mammalian target rapamycin (mTOR) signaling axis weaken RFA-mediated effect. In addition, synthesis arginylglycylaspartic acid (RGD)-lipid nanoparticles (LNPs) targeting cell-intrinsic enhanced Conclusion therapeutic HCC, via RGD-LNPs provides insight into clinical combating malignant progression cancer.

Language: Английский

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ALKBH5 enhances lipid metabolism reprogramming by increasing stability of FABP5 to promote pancreatic neuroendocrine neoplasms progression in an m6A-IGF2BP2-dependent manner

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

Published: Oct. 19, 2023

Abstract The process of post-transcriptional regulation has been recognized to be significantly impacted by the presence N 6-methyladenosine (m6A) modification. As an m6A demethylase, ALKBH5 shown contribute progression different cancers increasing expression several oncogenes. Hence, a better understanding key targets in cancer cells could potentially lead development new therapeutic targets. However, specific role pancreatic neuroendocrine neoplasms (pNENs) remains largely unknown. Here, we demonstrated that was up-regulated pNENs and played critical tumor growth lipid metabolism. Mechanistically, over-expression found increase FABP5 m6A- IGF2BP2 dependent manner, leading disorders Additionally, activate PI3K/Akt/mTOR signaling pathway, resulting enhanced metabolism proliferation abilities. In conclusion, our study uncovers ALKBH5/IGF2BP2/FABP5/mTOR axis as mechanism for aberrant modification highlights molecular basis strategies treatment. Graphical

Language: Английский

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Microenvironmental changes in familial adenomatous polyposis during colorectal cancer carcinogenesis

Cancer Letters, Journal Year: 2024, Volume and Issue: 589, P. 216822 - 216822

Published: March 21, 2024

Language: Английский

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Theoretical Framework and Emerging Challenges of Lipid Metabolism in Cancer

Seminars in Cancer Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Elevated lipid metabolism is one of hallmarks malignant tumors. Lipids not only serve as essential structural components biological membranes but also provide energy and substrates for the proliferation cancer cells tumor growth. Cancer meet their needs by coordinating processes absorption, synthesis, transport, storage, catabolism. As research in this area continues to deepen, numerous new discoveries have emerged, making it crucial scientists stay informed about developments metabolism. In review, we first discuss relevant concepts theories or assumptions that help us understand -based therapies. We then systematically summarize latest advancements including mechanisms, novel targets, up-to-date pre-clinical clinical investigations anti-cancer treatment with targeted drugs. Finally, emphasize emerging directions therapeutic strategies, future prospective challenges. This review aims insights guidance field

Language: Английский

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Role of Adiponectin in Regulating Cytokines and Its Contribution to the Occurrence and Progression of Clinical Mastitis in Holstein Cows

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2898 - 2898

Published: March 22, 2025

Cytokines are crucial in various physiological and pathological processes, especially inflammatory diseases mammals. However, the comprehensive identification of cytokines their potential regulatory functions mammary glands Holstein cows suffering from clinical mastitis (CM) remains only partially understood. This study aimed to systematically identify biological processes (BPs) differentially expressed proteins (DEPs) associated with explore through analysis previously obtained data data-independent acquisition (DIA) proteomics. We confirmed that dynamic balance between pro- anti-inflammatory factors is closely dairy mastitis. A total 4 BPs, comprising 75 upregulated 16 downregulated DEPs, were identified, particularly relation adiponectin (ADIPOQ), which strongly interacts other DEPs participates peroxisome proliferator-activated receptor (PPAR) adipocytokine signaling pathways. Immunohistochemical immunofluorescence staining revealed ADIPOQ was predominantly localized cytoplasm epithelial cells. Moreover, expression levels mRNA protein CM group notably reduced compared those healthy group. mechanism action suggested, findings indicating a decrease could potentially worsen inflammation CM. These results offer novel insights into mechanisms may benefit prevention treatment

Language: Английский

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Formononetin suppresses colitis-associated colon cancer by targeting lipid synthesis and mTORC2/Akt signaling

Phytomedicine, Journal Year: 2025, Volume and Issue: 142, P. 156665 - 156665

Published: May 2, 2025

Language: Английский

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NAP1L1 degradation by FBXW7 reduces the deubiquitination of HDGF-p62 signaling to stimulate autophagy and induce primary cisplatin chemosensitivity in nasopharyngeal carcinoma

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: May 26, 2025

Nucleosome assembly protein 1-like 1 (NAP1L1) has been implicated in promoting tumor cell proliferation. However, its role regulating autophagy tumors, including nasopharyngeal carcinoma (NPC), remains unclear. In this study, we observed that autophagy-inducing agents reduced NAP1L1 levels without affecting mRNA expression. Reduced enhanced autophagosome formation and maturation, thereby cisplatin (DDP) chemosensitivity both vitro vivo NPC models. Mechanistically, impaired the recruitment of ubiquitin-specific protease 14 (USP14), limiting deubiquitination heparin-binding growth factor (HDGF) decreasing HDGF levels. turn, suppressed USP14-mediated p62 deubiquitination, leading to further declines Notably, F-box WD repeat domain-containing 7 (FBXW7), an inhibitory E3 ubiquitin ligase, directly interacted with ubiquitinated NAP1L1, degradation. This degradation triggered DDP by disrupting NAP1L1-induced HDGF/p62 signaling. Clinically, expression was inversely correlated FBXW7 tissue samples. Patients exhibiting high low had poorest survival outcomes. Our findings demonstrate FBXW7-mediated suppresses HDGF-p62 signaling, inducing enhancing chemosensitivity. These results underscore potential as therapeutic targets for treatment.

Language: Английский

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High mobility group A1 (HMGA1) promotes the tumorigenesis of colorectal cancer by increasing lipid synthesis

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Nov. 15, 2024

Metabolic reprogramming is a hallmark of cancer, enabling tumor cells to meet the high energy and biosynthetic demands required for their proliferation. High mobility group A1 (HMGA1) structural transcription factor frequently overexpressed in human colorectal cancer (CRC). Here, we show that HMGA1 promotes CRC progression by driving lipid synthesis AOM/DSS-induced mouse model. Using conditional knockout (Hmga1△IEC) knock-in (Hmga1IEC-OE/+) models, demonstrate enhances cell proliferation accelerates development upregulating fatty acid synthase (FASN). Mechanistically, increases transcriptional activity sterol regulatory element-binding protein 1 (SREBP1) on FASN promoter, leading increased accumulation intestinal epithelial cells. Moreover, high-fat diet exacerbates Hmga1△IEC mice, while pharmacological inhibition orlistat reduces growth Hmga1IEC-OE/+ mice. Our findings suggest targeting metabolism could offer promising therapeutic strategy CRC. crucial progression. authors (CRC) model, enhancing via upregulation (FASN), inhibiting growth, suggesting potential avenues.

Language: Английский

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Neuronal fatty acid-binding protein enhances autophagy and suppresses amyloid-β pathology in a Drosophila model of Alzheimer’s disease

PLoS Genetics, Journal Year: 2024, Volume and Issue: 20(11), P. e1011475 - e1011475

Published: Nov. 19, 2024

Fatty acid-binding proteins (FABPs) are small cytoplasmic involved in intracellular lipid transport and bind free fatty acids, cholesterol, retinoids. FABP3, the major neuronal FABP adult brain, is upregulated CSF of patients with Alzheimer’s disease (AD). However, precise role FABPs AD pathogenesis remains unclear. This study investigates contribution fabp, Drosophila homolog FABP3 FABP7, to amyloid β (Aβ) pathology using a model. Neuronal knockdown fabp shortened lifespan flies increased age-related protein aggregates brain. In an model, neurons Aβ accumulation Aβ-induced neurodegeneration, whereas overexpression ameliorated pathology. Notably, stimulated autophagy, which was inhibited by Eip75B , peroxisome proliferator-activated receptor (PPAR). The PPAR activator rosiglitazone restored autophagy impaired reduced knockdown-induced aggregation cell death. Furthermore, either or wing imaginal disc fly brain expression Atg6 Atg8a . Additionally, treatment model polyunsaturated such as docosahexaenoic acid linoleic acid, partially alleviated death developing eye, flux, aggregation, attenuated Our results suggest that plays important maintaining homeostasis during aging protects from enhancing through pathway. These findings highlight potential importance function pathogenesis.

Language: Английский

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