AMPK: The Energy Sensor at the Crossroads of Aging and Cancer

Seminars in Cancer Biology, Journal Year: 2024, Volume and Issue: 106-107, P. 15 - 27

Published: Aug. 26, 2024

Language: Английский

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LKB1 biology: assessing the therapeutic relevancy of LKB1 inhibitors

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: June 6, 2024

Abstract Liver Kinase B1 (LKB1), encoded by Serine-Threonine 11 ( STK11 ), is a master kinase that regulates cell migration, polarity, proliferation, and metabolism through downstream adenosine monophosphate-activated protein (AMPK) AMPK-related signalling. Since genetic screens identified mutations in Peutz-Jeghers Syndrome, mutants have been implicated tumourigenesis labelling it as tumour suppressor. In support of this, several compounds reduce burden upregulating LKB1 signalling, LKB1-AMPK agonists are cytotoxic to cells. However, certain contexts, its role cancer paradoxical promotes survival mediating resistance against metabolic oxidative stressors. deficiency has also enhanced the selectivity cytotoxicity therapies. Taken together, there need develop LKB1-specific pharmacological compounds, but prior developing inhibitors, further work needed understand activity regulation. investigating strenuous cell/tissue type, signalling pathway, STE-20-related adaptor (STRAD) binding, Mouse 25-STRAD splicing variants, nucleocytoplasmic shuttling, post-translational modifications, conformation impact functional status LKB1. For these reasons, guidelines standardize experimental strategies study activity, associate proteins, spliced isoforms, regulation upmost importance development Therefore, assess therapeutic relevancy this review summarizes physiology, highlights contributors activation, outlines benefits risks associated with targeting

Language: Английский

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Autophagy flux in bladder cancer: Cell death crosstalk, drug and nanotherapeutics

Cancer Letters, Journal Year: 2024, Volume and Issue: 591, P. 216867 - 216867

Published: April 7, 2024

Language: Английский

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The MCM6-c-Myc positive feedback loop mediates bladder cancer progression and cisplatin resistance

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 296, P. 139777 - 139777

Published: Jan. 11, 2025

Language: Английский

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COTI-2 suppresses the malignancy of bladder cancer by inducing apoptosis via the AMPK-mTOR signaling pathway.

PubMed, Journal Year: 2025, Volume and Issue: 28(3), P. 240 - 246

Published: Jan. 1, 2025

COTI-2, an innovative oral homocysteine, has shown promising antitumor results on multiple types of cancer. However, its effects in treating bladder cancer (BCa) and the underlying molecular mechanisms have not been elucidated. The present study aimed to explore COTI-2 BCa potential mechanisms. cell lines, including 5637 T24 were treated with at concentrations 0.5 1 μM, respectively. Cell Counting Kit (CCK)-8 assay, colony formation apoptosis transwell migration invasion assay conducted evaluate cells. Western blotting, H&E, immunohistochemical staining, immunofluorescence analysis performed investigate Moreover, a xenograft model nude mice using cells was generated determine activities vivo. highly inhibited proliferation cells, induced their apoptosis. it efficiently suppressed Additionally, subcutaneous showed that treatment tumor growth by inducing We also found promoted presumably through activating AMPK/mTOR pathway. Our data suggest effectively reduces malignancy BCa, probably via signaling These highlight as therapeutic agent for BCa.

Language: Английский

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Mitochondria-associated non-coding RNAs and their impact on drug resistance

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 26, 2025

Drug resistance is a prevalent challenge in clinical disease treatment, often leading to relapse and poor prognosis. Therefore, it crucial gain deeper understanding of the molecular mechanisms underlying drug develop targeted strategies for its effective prevention management. Mitochondria, as vital energy-producing organelles within cells, have been recognized key regulators sensitivity. Processes such mitochondrial fission, fusion, mitophagy, changes membrane potential, reactive oxygen species (ROS) accumulation, oxidative phosphorylation (OXPHOS) are all linked Non-coding RNAs (ncRNAs) enriched mitochondria (mtncRNA), whether transcribed from DNA (mtDNA) or nucleus transported mitochondria, can regulate transcription translation mtDNA, thus influencing function, including substance exchange energy metabolism. This, turn, directly indirectly affects cellular sensitivity drugs. This review summarizes types mtncRNAs associated with regulating resistance. Our aim provide insights overcoming by modulating mtncRNAs.

Language: Английский

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LIMA1 inhibits cisplatin resistance and malignant biological behavior of bladder cancer cells by suppressing the Wnt/β-catenin pathway

BMC Medical Genomics, Journal Year: 2025, Volume and Issue: 18(1)

Published: April 23, 2025

This study aimed to explore the effect of LIM domain and actin binding 1 (LIMA1) on bladder cancer (BCa) cells investigate its underlying molecular mechanisms. The expression LIMA1 gene in clinical BCa tissue samples cell models was detected using real-time quantitative PCR western blot. Subsequently, knockdown experiments were performed exclusively J82 line, while overexpression conducted only cisplatin-resistant J82/CR line. proliferation assessed by colony formation assay. Cisplatin resistance evaluated MTT Migration invasion tested Transwell Additionally, levels key proteins Wnt/β-catenin signaling pathway examined blotting. We found that underexpressed tissues (P < 0.01). Overexpression inhibited proliferation, migration, invasion, epithelial-mesenchymal transition 0.01) improved their cisplatin 0.01), whereas knocking down produced opposite results Furthermore, could suppress activation this partially reversed anti-tumor effects inhibit malignant biological behavior weaken negatively regulating pathway. Our findings provide new insights for treatment BCa.

Language: Английский

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Matrine induces autophagic cell death by triggering ROS/AMPK/mTOR axis and apoptosis in multiple myeloma

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116738 - 116738

Published: May 16, 2024

Despite significant advancements in multiple myeloma (MM) treatment recent years, most patients will eventually develop resistance or experience relapse. Matrine, a primary active compound of traditional Chinese medicinal herb Sophora flavescens Ait, has been found to have anti-tumor properties various types malignant tumors. Whether autophagy plays crucial role the anti-MM effect matrine remain unknown. Herein, we that could trigger apoptosis and cell cycle arrest, meanwhile induce MM cells vitro. We further ascertained by using ATG5 siRNA inhibitor spautin-1, which partially reversed matrine's inhibitory on cells. Conversely, combination with inducer rapamycin enhanced their activity. These findings suggest induced can lead death Further mechanism investigation revealed increased levels reactive oxygen species (ROS) AMPKα1 phosphorylation decreased mTOR Additionally, co-treatment ROS scavenger N-acetyl-1-cysteine weakened increase was matrine. Finally, demonstrated synergistic against xenograft mouse model. Collectively, our provided novel insights into efficacy induces triggering ROS/AMPK/mTOR axis cells, combinatorial may be promising therapeutic strategy MM.

Language: Английский

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Targeting autophagy in urological system cancers: From underlying mechanisms to therapeutic implications

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(6), P. 189196 - 189196

Published: Oct. 18, 2024

Language: Английский

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The Role of Adenosine in Overcoming Resistance in Sarcomas

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12209 - 12209

Published: Nov. 14, 2024

Resistance to systemic therapies in sarcomas poses a significant challenge improving clinical outcomes. Recent research has concentrated on the tumor microenvironment’s role sarcoma progression and treatment resistance. This microenvironment comprises variety of cell types signaling molecules that influence behavior, including proliferation, metastasis, resistance therapy. Adenosine, abundant microenvironment, been implicated promoting immunosuppression chemoresistance. Targeting adenosine receptors associated pathways offers novel approach enhancing immune responses against tumors, potentially immunotherapy outcomes cancers, sarcomas. Manipulating also shows promise overcoming chemotherapy these tumors. Clinical trials investigating receptor antagonists have fueled interest this pathway for treatment. Ultimately, comprehensive understanding vascular microenvironments, as well pathway, may open new avenues sarcoma. Further studies are crucial validate findings optimize therapeutic strategies, particularly osteosarcoma. study provides literature review exploring potential

Language: Английский

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