Mechanisms of drug resistance in nutrient-depleted colorectal cancer cells: insights into lysosomal and mitochondrial drug sequestration DOI Creative Commons
Shingo Kose, Aliye Ezgi Güleç Taşkıran

Biology Open, Journal Year: 2024, Volume and Issue: 13(10)

Published: July 15, 2024

ABSTRACT This Review delves into the mechanisms behind drug resistance in colorectal cancer (CRC), particularly examining role of nutrient depletion and its contribution to multidrug (MDR). The study highlights metabolic adaptations cells as well under low availability, including shifts glycolysis lipid metabolism. It emphasizes significance MDR1 encoded efflux transporter, P-glycoprotein (P-gp/B1), mediating how pathways such HIF1α, AKT, mTOR influence expression P-gp/B1 limited availability. Additionally, explores dual roles autophagy sensitivity conditions. further investigates involvement lysosomes mitochondria, focusing on their sequestration challenges posed by lysosomal entrapment facilitated non-enzymatic processes ABC transporters like P-gp/B1. Finally, underscores importance understanding interplay between sequestration, functions, depletion, gene modulation. suggests innovative strategies, structural modifications nanotechnology, promising approaches overcoming therapy.

Language: Английский

Engineered Extracellular Vesicles Derived from Juvenile Mice Enhance Mitochondrial Function in the Aging Bone Microenvironment and Achieve Rejuvenation DOI

Jiaqian Zheng,

Yipeng Ren,

Junhua Ke

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

Aging-related bone degeneration and impaired healing capacity remain significant challenges in regenerative medicine, necessitating innovative, efficient, targeted strategies to restore health. Here, we engineered extracellular vesicles (EVs) derived from the serum of pretreated juvenile mice, with goals reversing aging, enhancing osteogenic potential, increasing bioavailability rejuvenate aging environment. First, established models representing different phases identify EV type highest potential for improving microenvironment older individuals. Second, employed DSS6 targeting enhance biological effects selected EVs vivo. The effectively repair sites promoted fracture more than unmodified mice. RNA sequencing revealed that translocase outer mitochondrial membrane 7 (Tomm7) is crucial underlying mechanism. Silencing Tomm7 significantly diminished positive regulatory EVs. Specifically, may function cells by activating Tomm7-mediated Pink1/Parkin mitophagy pathway, promoting stemness recovery marrow stromal (BMSCs) adverse conditions microenvironment. Overall, developed mice offer an alternative approach treating bones. identified mechanisms provide a valuable reference precision treatment bones future.

Language: Английский

Citations

0
Identification of necroptosis & mitophagy-related key genes and their prognostic value in colorectal cancer DOI Creative Commons
Xiuling Zhang, Meng Li, Tingjian Zu

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 4, 2025

Language: Английский

Citations

0
Galectin-8 drives ERK-dependent mitochondrial fragmentation, perinuclear relocation and mitophagy, with metabolic adaptations for cell proliferation DOI Creative Commons
Adely de la Peña, Cláudio Retamal,

Francisca Pérez-Molina

et al.

European Journal of Cell Biology, Journal Year: 2025, Volume and Issue: unknown, P. 151488 - 151488

Published: April 1, 2025

Mitochondria adapt to the cell proliferative demands induced by growth factors through dynamic changes in morphology, distribution, and metabolic activity. Galectin-8 (Gal-8), a carbohydrate-binding protein that promotes proliferation transactivating EGFR-ERK signaling pathway, is overexpressed several cancers. However, its impact on mitochondrial dynamics during remains unknown. Using MDCK RPTEC kidney epithelial cells, we demonstrate Gal-8 induces fragmentation perinuclear redistribution. Additionally, mitochondria adopt donut-shaped morphologies, live-cell imaging with two Keima-based reporters demonstrates Gal-8-induced mitophagy. ERK inhibition abrogates all these proliferation. Studies established mutant versions of CHO cells reveal response require interactions between N-terminal carbohydrate recognition domain α-2,3-sialylated N-glycans at surface. DRP1, key regulator fission, becomes phosphorylated or an ERK-dependent manner, mediating Bafilomycin A proliferation, suggesting mitophagy serves as adaptation demands. Functional analysis under stimulation shows maintain active electron transport chain, partially uncoupled from ATP synthesis, increased membrane potential, indicative healthy mitochondria. Meanwhile, exhibit extracellular acidification rate lactate production via aerobic glycolysis, hallmark state. Our findings integrate adaptations potential implications for physiology, disease, therapeutic strategies.

Language: Английский

Citations

0
Decoding the Neuroimmune Axis in Colorectal Cancer: From Neural Circuitry to Therapeutic Innovation DOI
Ying Li, Suk‐Kyun Yang,

Yongyin Zhang

et al.

Cytokine & Growth Factor Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
Kynurenine in IDO1high cancer cell-derived extracellular vesicles promotes angiogenesis by inducing endothelial mitophagy in ovarian cancer DOI Creative Commons
Ying Xiang, Xiaocui Zheng,

Xiaoqian Zhang

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 11, 2024

Abstract Background Mitophagy, a prominent cellular homeostasis process, has been implicated in modulating endothelial cell function. Emerging evidence suggests that extracellular vesicles (EVs) participate intercellular communication, which could modulate tumor angiogenesis, hallmark of ovarian cancer (OC) progression. However, the underlying mechanisms through how EVs regulate mitophagy associated with angiogenesis during OC development remain obscure. Methods The effect cell-derived on and its correlation were explored by vitro vivo experiments. Multi-omics integration analysis was employed to identify potential regulatory mitophagy, is involved development. These insights then further corroborated additional An orthotopic mouse model constructed assess antiangiogenic therapeutic Indoleamine 2,3 dioxygenase-1 (IDO1) inhibitor. Results Cancer promoted via activation contributing growth metastasis OC. aberrantly high expression IDO1 mediated abnormal tryptophan metabolism cells secretion l -kynurenine (L-kyn)-enriched EVs, levels L-kyn isolated from both tissues patient plasma derived elevated nicotinamide adenine dinucleotide (NAD +) delivering L-kyn. Besides, upregulated sirt3 increasing acetylation modification. findings are crucial for promoting correlated angiogenesis. Notably, be suppressed inhibitor model. Conclusions Together, our unveil mechanism indicate clinical relevance EV enriched as biomarker tumorigenesis Additionally, inhibitors might become an alternative option adjuvant therapy. Graphical

Language: Английский

Citations

3
Pharmacological modulation of mitochondrial function as novel strategies for treating intestinal inflammatory diseases and colorectal cancer DOI Creative Commons
Boya Wang,

Xinrui Guo,

Lanhui Qin

et al.

Journal of Pharmaceutical Analysis, Journal Year: 2024, Volume and Issue: unknown, P. 101074 - 101074

Published: Aug. 1, 2024

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal disease, has become major global health issue. Individuals with IBD face an elevated risk of developing colorectal cancer (CRC), recent studies have indicated that mitochondrial dysfunction plays pivotal role in the pathogenesis both CRC. This review covers CRC, focusing on dysfunction, explores pharmacological targets strategies for addressing conditions by modulating function. Additionally, advancements modulation treating encompassing damage, release DNA (mtDNA), impairment mitophagy, are thoroughly summarized. The also provides systematic overview natural compounds (such as flavonoids, alkaloids, diterpenoids), Chinese medicines, microbiota, which can alleviate attenuate progression CRC In future, it will be imperative to develop more practical methodologies real-time monitoring accurate detection function, greatly aid scientists identifying effective agents through

Language: Английский

Citations

3
A Narrative Review: Immunometabolic Interactions of Host–Gut Microbiota and Botanical Active Ingredients in Gastrointestinal Cancers DOI Open Access

Shanlan Li,

Wuwen Feng, Jiaqi Wu

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 9096 - 9096

Published: Aug. 22, 2024

The gastrointestinal tract is where the majority of gut microbiota settles; therefore, composition and changes in metabolites, as well their modulatory effects on immune system, have a very important impact development diseases. purpose this article was to review role host environment immunometabolic system summarize beneficial botanical active ingredients cancer, so provide prospective insights for prevention treatment A literature search performed PubMed database with keywords “gastrointestinal cancer”, “gut microbiota”, “immunometabolism”, “SCFAs”, “bile acids”, “polyamines”, “tryptophan”, “bacteriocins”, “immune cells”, “energy metabolism”, “polyphenols”, “polysaccharides”, “alkaloids”, “triterpenes”. influenced disorders, whereas such SCFAs, bacteriocins, could impede cancers polyamine-, tryptophan-, bile acid-induced carcinogenic mechanisms. GPRCs, HDACs, FXRs, AHRs were receptor signals microbial metabolites influencing cancer. Botanical exerted positive cancer by microbes modulating metabolism. Gastrointestinal be ameliorated altering environment, administering treatment, stimulating or blocking metabolism signaling molecules. Despite extensive growing research microbiota, it appeared represent more an indicator health status associated adequate fiber intake than autonomous causative factor This study detailed pathogenesis used hope providing inspiration into simpler, safer, effective pathways therapeutic agents field.

Language: Английский

Citations

2
Solute carrier family 35 member A2 regulates mitophagy through the PI3K/AKT/mTOR axis, promoting the proliferation, migration, and invasion of osteosarcoma cells DOI
Xiaohui Luo,

Jiongfeng Zhang,

Chong Guo

et al.

Gene, Journal Year: 2023, Volume and Issue: 898, P. 148110 - 148110

Published: Dec. 25, 2023

Language: Английский

Citations

6
The oncogenic roles of GPR176 in ovarian cancer: a molecular target for aggressiveness and gene therapy DOI Creative Commons
Ning Yang,

Wen-Jing Yun,

Zheng‐Guo Cui

et al.

Journal of Obstetrics and Gynaecology, Journal Year: 2024, Volume and Issue: 44(1)

Published: June 4, 2024

Background At present, the discovery of new biomarkers is great significance for early diagnosis, treatment and prognosis assessment ovarian cancer. Previous findings indicated that aberrant G-protein-coupled receptor 176 (GPR176) expression might contribute to tumorigenesis subsequent progression. However, GPR176 molecular mechanisms in cancer had not been investigated.

Language: Английский

Citations

1
GPR176 promotes fibroblast-to-myofibroblast transition in organ fibrosis progression DOI Creative Commons

Yasuo Okamoto,

Keisuke Kitakaze, Yasuhiro Takenouchi

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2024, Volume and Issue: 1871(7), P. 119798 - 119798

Published: July 22, 2024

Fibrosis is characterized by excessive deposition of extracellular matrix proteins, particularly collagen, caused myofibroblasts in response to chronic inflammation. Although G protein-coupled receptors (GPCRs) are among the targets current antifibrotic drugs, no drug has yet been approved stop fibrosis progression. Herein, we aimed identify GPCRs with profibrotic effects. In gene expression analysis mouse lungs induced fibrosis, eight were identified, showing a >2-fold increase mRNA after induction. Among them, focused on Gpr176 owing its significant correlation myofibroblast marker α-smooth muscle actin (αSMA), factor transforming growth β1 (TGFβ1), and collagen human lung database. Similar model, increased was also observed other organs affected including kidney, liver, heart, suggesting role across various organs. Furthermore, fibroblasts abundantly expressed compared alveolar epithelial cells, endothelial macrophages fibrotic lung. GPR176 unaffected TGFβ1 stimulation rat renal fibroblast NRK-49 whereas knockdown siRNA reduced TGFβ1-induced αSMA, fibronectin, as well Smad2 phosphorylation. This suggested that regulates activation. Consequently, acts manner, inhibiting activity could potentially prevent differentiation improve fibrosis. Developing inverse agonist or allosteric modulator promising therapeutic approach for

Language: Английский

Citations

1