Adipocyte and lipid metabolism in cancer drug resistance

Journal of Clinical Investigation, Journal Year: 2019, Volume and Issue: 129(8), P. 3006 - 3017

Published: July 1, 2019

Development of novel and effective therapeutics for treating various cancers is probably the most congested challenging enterprise pharmaceutical companies. Diverse drugs targeting malignant nonmalignant cells receive clinical approval each year from FDA. Targeting cancer unavoidably changes tumor microenvironment, cellular molecular components relentlessly alter in response to drugs. Cancer often reprogram their metabolic pathways adapt environmental challenges facilitate survival, proliferation, metastasis. While cells' dependence on glycolysis energy production well studied, roles adipocytes lipid reprogramming supporting growth, metastasis, drug responses are less understood. This Review focuses emerging mechanisms involving metabolism altering treatment. In particular, we discuss underlying cancer-associated resistance.

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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YAP and TAZ: a signalling hub of the tumour microenvironment

Nature reviews. Cancer, Journal Year: 2019, Volume and Issue: 19(8), P. 454 - 464

Published: July 3, 2019

Language: Английский

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Crosstalk between mechanotransduction and metabolism

Nature Reviews Molecular Cell Biology, Journal Year: 2020, Volume and Issue: 22(1), P. 22 - 38

Published: Nov. 13, 2020

Language: Английский

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Pathway-based classification of glioblastoma uncovers a mitochondrial subtype with therapeutic vulnerabilities

Nature Cancer, Journal Year: 2021, Volume and Issue: 2(2), P. 141 - 156

Published: Jan. 11, 2021

Language: Английский

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Analysis of the role of the Hippo pathway in cancer

Journal of Translational Medicine, Journal Year: 2019, Volume and Issue: 17(1)

Published: April 8, 2019

Cancer is a serious health issue in the world due to large body of cancer-related human deaths, and there no current treatment available efficiently treat disease as tumor often diagnosed at stage. Moreover, cells are resistant chemotherapy, radiotherapy, molecular-targeted therapy. Upon further knowledge mechanisms tumorigenesis, aggressiveness, metastasis, resistance treatments, it necessary detect an earlier stage for better response The hippo pathway possesses unique capacity lead tumorigenesis. Mutations altered expression its core components (MST1/2, LATS1/2, YAP TAZ) promote migration, invasion, malignancy cancer cells. biological significance deregulation have received interests past few years. Further understanding will be responsible treatment. In this review, we try discover function different diversity cancers, discuss how Hippo contributes other cellular signaling pathways. Also, describe microRNAs, circRNAs, ZNFs regulate process cancer. It find new therapy strategies

Language: Английский

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The Warburg Effect 97 Years after Its Discovery

Cancers, Journal Year: 2020, Volume and Issue: 12(10), P. 2819 - 2819

Published: Sept. 30, 2020

The deregulation of the oxidative metabolism in cancer, as shown by increased aerobic glycolysis and impaired phosphorylation (Warburg effect), is coordinated genetic changes leading to activation oncogenes loss oncosuppressor genes. understanding metabolic cancer cells necessary prevent cure cancer. In this review, we illustrate comment principal molecular variations cells, involved their anomalous behavior, that include modifications metabolism, promote a decrease oxygen consumption susceptibility correlations defective mitochondria, relationships between Warburg effect tumor therapy, recent studies reevaluate effect. Taken together, these observations indicate an epiphenomenon transformation process essential for development malignancy.

Language: Английский

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Tuning immunity through tissue mechanotransduction

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 23(3), P. 174 - 188

Published: Aug. 16, 2022

Language: Английский

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A combat with the YAP/TAZ-TEAD oncoproteins for cancer therapy

Theranostics, Journal Year: 2020, Volume and Issue: 10(8), P. 3622 - 3635

Published: Jan. 1, 2020

The transcriptional co-regulators YAP and TAZ pair primarily with the TEAD family of transcription factors to elicit a gene expression signature that plays prominent role in cancer development, progression metastasis. endow cells various oncogenic traits such they sustain proliferation, inhibit apoptosis, maintain stemness, respond mechanical stimuli, engineer metabolism, promote angiogenesis, suppress immune response develop resistance therapies. Therefore, inhibiting YAP/TAZ- is an attractive viable option for novel therapy. It exciting know many drugs already clinic restrict YAP/TAZ activities several inhibitors are currently under development. We have classified YAP/TAZ-inhibiting into three groups. Group I act on upstream regulators stimulators activities. Many potential be repurposed as indirect treat solid cancers. II modalities directly or TEADs disrupt their interaction; targeting has emerged YAP/TAZ, major mediators programs. can also leveraged using small molecules activate YAP/TAZ-dependent use regenerative medicine. III focus one downstream target genes. With right strategy impetus, it not far-fetched expect group drug combat cancers near future.

Language: Английский

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Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: July 31, 2023

Abstract Cellular mechanotransduction, a critical regulator of numerous biological processes, is the conversion from mechanical signals to biochemical regarding cell activities and metabolism. Typical cues in organisms include hydrostatic pressure, fluid shear stress, tensile force, extracellular matrix stiffness or tissue elasticity, viscosity. Mechanotransduction has been expected trigger multiple such as embryonic development, repair regeneration. However, prolonged excessive stimulation can result pathological multi-organ fibrosis, tumorigenesis, cancer immunotherapy resistance. Although associations between normal homeostasis diseases have identified, regulatory mechanisms among different are not yet comprehensively illustrated, no effective therapies currently available targeting cue-related signaling. This review systematically summarizes characteristics typical conditions with updated evidence. The key effectors responding stimulations listed, Piezo channels, integrins, Yes-associated protein (YAP) /transcriptional coactivator PDZ-binding motif (TAZ), transient receptor potential vanilloid 4 (TRPV4). We also reviewed signaling pathways, therapeutic targets cutting-edge clinical applications related cues.

Language: Английский

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