The sirtuin family in health and disease

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Dec. 29, 2022

Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, involved numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles members SIRT family health disease conditions. Notably, this protein plays a variety important cellular biology such as inflammation, metabolism, oxidative stress, apoptosis, etc., thus, it is considered potential therapeutic target for different kinds pathologies including cancer, cardiovascular disease, respiratory other Moreover, identification modulators exploring functions these prompted increased efforts discover new small molecules, which can modify activity. Furthermore, several randomized controlled trials indicated that interventions might affect expression human samples, supplementation diverse impact on physiological function participants. In review, we introduce history structure family, discuss molecular mechanisms elaborate regulatory SIRTs summarize inhibitors activators, review related clinical studies.

Language: Английский

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The Hippo signalling pathway and its implications in human health and diseases

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Nov. 8, 2022

Abstract As an evolutionarily conserved signalling network, the Hippo pathway plays a crucial role in regulation of numerous biological processes. Thus, substantial efforts have been made to understand upstream signals that influence activity pathway, as well its physiological functions, such cell proliferation and differentiation, organ growth, embryogenesis, tissue regeneration/wound healing. However, dysregulation can cause variety diseases, including cancer, eye cardiac pulmonary renal hepatic immune dysfunction. Therefore, therapeutic strategies target dysregulated components might be promising approaches for treatment wide spectrum diseases. Here, we review key critical functions controlled by pathway. Additionally, diseases associated with alterations potential therapies targeting will discussed.

Language: Английский

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Metabolic programming and immune suppression in the tumor microenvironment

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(3), P. 421 - 433

Published: Feb. 16, 2023

Language: Английский

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The Hippo pathway in cancer: YAP/TAZ and TEAD as therapeutic targets in cancer

Clinical Science, Journal Year: 2022, Volume and Issue: 136(3), P. 197 - 222

Published: Feb. 1, 2022

Abstract Tumorigenesis is a highly complex process, involving many interrelated and cross-acting signalling pathways. One such pathway that has garnered much attention in the field of cancer research over last decade Hippo pathway. Consisting two antagonistic modules, plays an integral role both tumour suppressive oncogenic processes, generally via regulation diverse set genes involved range biological functions. This review discusses history within context explores some most recent discoveries as to how this critical transducer cellular can influence progression. A special focus on various efforts therapeutically target key effectors preclinical clinical settings.

Language: Английский

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Molecular mechanisms of tumor resistance to radiotherapy

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: June 15, 2023

Abstract Background Cancer is the most prevalent cause of death globally, and radiotherapy considered standard care for solid tumors, including lung, breast, esophageal, colorectal cancers glioblastoma. Resistance to radiation can lead local treatment failure even cancer recurrence. Main body In this review, we have extensively discussed several crucial aspects that resistance therapy, radiation-induced DNA damage repair, cell cycle arrest, apoptosis escape, abundance stem cells, modification cells their microenvironment, presence exosomal non-coding RNA, metabolic reprogramming, ferroptosis. We aim focus on molecular mechanisms in relation these discuss possible targets improve outcomes. Conclusions Studying responsible its interactions with tumor environment will help responses radiotherapy. Our review provides a foundation identify overcome obstacles effective

Language: Английский

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Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Oct. 2, 2023

Abstract Despite centuries since the discovery and study of cancer, cancer is still a lethal intractable health issue worldwide. Cancer-associated fibroblasts (CAFs) have gained much attention as pivotal component tumor microenvironment. The versatility sophisticated mechanisms CAFs in facilitating progression been elucidated extensively, including promoting angiogenesis metastasis, inducing drug resistance, reshaping extracellular matrix, developing an immunosuppressive Owing to their robust tumor-promoting function, are considered promising target for oncotherapy. However, highly heterogeneous group cells. Some subpopulations exert inhibitory role growth, which implies that CAF-targeting approaches must be more precise individualized. This review comprehensively summarize origin, phenotypical, functional heterogeneity CAFs. More importantly, we underscore advances strategies clinical trials CAF various cancers, also progressions immunotherapy.

Language: Английский

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Designing bioresponsive nanomaterials for intracellular self-assembly

Nature Reviews Chemistry, Journal Year: 2022, Volume and Issue: 6(5), P. 320 - 338

Published: April 1, 2022

Language: Английский

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Artificial intelligence-based multi-omics analysis fuels cancer precision medicine

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 88, P. 187 - 200

Published: Dec. 31, 2022

Language: Английский

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Molecular basis for redox control by the human cystine/glutamate antiporter system xc−

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Dec. 8, 2021

Cysteine plays an essential role in cellular redox homoeostasis as a key constituent of the tripeptide glutathione (GSH). A rate limiting step GSH synthesis is availability cysteine. However, circulating cysteine exists blood oxidised di-peptide cystine, requiring specialised transport systems for its import into cell. System xc

Language: Английский

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Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Sept. 17, 2022

Abstract Protein tyrosine kinases (PTKs) are a class of proteins with kinase activity that phosphorylate residues critical molecules in signaling pathways. Their basal function is essential for maintaining normal cell growth and differentiation. However, aberrant activation PTKs caused by various factors can deviate from the expected trajectory to an abnormal state, leading carcinogenesis. Inhibiting PTK could inhibit tumor growth. Therefore, inhibitors (TKIs), target-specific PTKs, have been used treating malignant tumors play significant role targeted therapy cancer. Currently, drug resistance main reason limiting TKIs efficacy The increasing studies indicated microenvironment, death resistance, metabolism, epigenetic modification metabolism were deeply involved development TKI besides PTK-related pathways gene mutations. Accordingly, it great significance study underlying mechanisms find solutions reverse improving Herein, we reviewed potential approaches overcome aiming provide theoretical basis TKIs.

Language: Английский

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