Natural compounds targeting YAP/TAZ axis in cancer: Current state of art and challenges DOI Creative Commons
Aviral Kumar, Bandari BharathwajChetty,

Mukesh Kumar Manickasamy

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 203, P. 107167 - 107167

Published: April 9, 2024

Cancer has become a burgeoning global healthcare concern marked by its exponential growth and significant economic ramifications. Though advancements in the treatment modalities have increased overall survival quality of life, there are no definite treatments for advanced stages this malady. Hence, understanding diseases etiologies underlying molecular complexities, will usher development innovative therapeutics. Recently, YAP/TAZ transcriptional regulation been immense interest due to their role development, tissue homeostasis oncogenic transformations. axis functions as coactivators within Hippo signaling cascade, exerting pivotal influence on processes such proliferation, regeneration, renewal. In cancer, YAP is overexpressed multiple tumor types associated with cancer stem cell attributes, chemoresistance, metastasis. Activation mirrors cellular "social" behavior, encompassing factors adhesion mechanical signals transmitted from structure surrounding extracellular matrix. Therefore, it presents vulnerability clogs tumors that could provide wide window therapeutic effectiveness. Natural compounds utilized extensively successful interventions management diverse chronic illnesses, including cancer. Owing capacity genes pathways, natural exhibit potential either adjuvant therapy or combination conventional options. review, we delineate nexus axis, present an alternate strategy target

Language: Английский

Harnessing the potential of hydrogels for advanced therapeutic applications: current achievements and future directions DOI Creative Commons

Peilin Lu,

Dongxue Ruan,

Meiqi Huang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: July 1, 2024

The applications of hydrogels have expanded significantly due to their versatile, highly tunable properties and breakthroughs in biomaterial technologies. In this review, we cover the major achievements potential therapeutic applications, focusing primarily on two areas: emerging cell-based therapies promising non-cell modalities. Within context cell therapy, discuss capacity overcome existing translational challenges faced by mainstream therapy paradigms, provide a detailed discussion advantages principal design considerations for boosting efficacy as well list specific examples different disease scenarios. We then explore drug delivery, physical intervention therapies, other areas (e.g., bioadhesives, artificial tissues, biosensors), emphasizing utility beyond mere delivery vehicles. Additionally, complement our latest progress clinical application outline future research directions, particularly terms integration with advanced biomanufacturing This review aims present comprehensive view critical insights into selection both tailored meet requirements diverse diseases situations.

Language: Английский

Citations

109
The opportunities and challenges in immunotherapy: Insights from the regulation of PD-L1 in cancer cells DOI Creative Commons
Qingyu Lin, Xingwen Wang, Ying Hu

et al.

Cancer Letters, Journal Year: 2023, Volume and Issue: 569, P. 216318 - 216318

Published: July 15, 2023

The immunosuppressive molecule programmed death-ligand 1 (PD-L1) is frequently upregulated in human cancers. Binding of PD-L1 to its receptor, death-1 (PD-1), on activated T cells facilitates cancer evade the host immune system. Antibody-based PD-1/PD-L1 inhibitors can inhibit interaction allowing reactivate cytotoxic eradicate advanced cells. However, majority patients fail respond anti-PD-1/PD-L1 therapies and molecular mechanisms for this remain poorly understood. Recent studies show that expression level tumor affect clinical efficacy checkpoint therapies. Thus, furthering our understanding regulatory will be critical improve response rates Here we review recent studies, primarily focusing regulate at transcriptional, post-transcriptional protein level, with purpose drive development more targeted effective

Language: Английский

Citations

55
Redox regulation: mechanisms, biology and therapeutic targets in diseases DOI Creative Commons
Bowen Li, Hui Ming, Siyuan Qin

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 7, 2025

Redox signaling acts as a critical mediator in the dynamic interactions between organisms and their external environment, profoundly influencing both onset progression of various diseases. Under physiological conditions, oxidative free radicals generated by mitochondrial respiratory chain, endoplasmic reticulum, NADPH oxidases can be effectively neutralized NRF2-mediated antioxidant responses. These responses elevate synthesis superoxide dismutase (SOD), catalase, well key molecules like nicotinamide adenine dinucleotide phosphate (NADPH) glutathione (GSH), thereby maintaining cellular redox homeostasis. Disruption this finely tuned equilibrium is closely linked to pathogenesis wide range Recent advances have broadened our understanding molecular mechanisms underpinning dysregulation, highlighting pivotal roles genomic instability, epigenetic modifications, protein degradation, metabolic reprogramming. findings provide foundation for exploring regulation mechanistic basis improving therapeutic strategies. While antioxidant-based therapies shown early promise conditions where stress plays primary pathological role, efficacy diseases characterized complex, multifactorial etiologies remains controversial. A deeper, context-specific signaling, particularly redox-sensitive proteins, designing targeted aimed at re-establishing balance. Emerging small molecule inhibitors that target specific cysteine residues proteins demonstrated promising preclinical outcomes, setting stage forthcoming clinical trials. In review, we summarize current intricate relationship disease also discuss how these insights leveraged optimize strategies practice.

Language: Английский

Citations

4
Discovery of 2,4-diaminopyrimidine derivatives as potent inhibitors of FAK capable of activating the Hippo pathway for the treatment of esophageal squamous cell carcinoma DOI
Xiao Wang,

Yin-Ru Li,

Ji Wu

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 287, P. 117328 - 117328

Published: Feb. 2, 2025

Language: Английский

Citations

3
Positive feedback between arginine methylation of YAP and methionine transporter SLC43A2 drives anticancer drug resistance DOI Creative Commons
Xialu Hong, Chenkai Huang, Hui Qian

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Yes-associated protein (YAP) activation confers resistance to chemotherapy and targeted therapy. Methionine participates in cellular processes by converting methyl donor for the methylation of DNA, RNA protein. However, it remains unclear whether methionine affects drug influencing YAP activity. In this study, we report that deprivation remarkably suppresses transcriptional activity YAP–TEAD cancer cells. promotes PRMT1-catalyzed asymmetric dimethylation at R124 (YAP R124me2a). Mimicking abolishes reduction effect methionine-restricted diet on YAP-induced resistance. activates transcription SLC43A2, transporter, increase uptake Knockdown SLC43A2 decreases level R124me2a. BCH, inhibitor sensitizes tumors anticancer drugs. Thus, our results unravel positive feedback between contributes Disrupting could be a potential strategy While deficiency can sensitize cells therapy, Here, authors discover loop present transporter is involved multiple therapies.

Language: Английский

Citations

2
The strategies to cure cancer patients by eradicating cancer stem-like cells DOI Creative Commons

Yansui Mai,

Jiyan Su,

Chuan Yang

et al.

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

Published: Oct. 18, 2023

Abstract Cancer stem-like cells (CSCs), a subpopulation of cancer cells, possess remarkable capability in proliferation, self-renewal, and differentiation. Their presence is recognized as crucial factor contributing to tumor progression metastasis. CSCs have garnered significant attention therapeutic focus an etiologic root treatment-resistant cells. Increasing evidence indicated that specific biomarkers, aberrant activated pathways, immunosuppressive microenvironment (TME), immunoevasion are considered the culprits occurrence maintenance properties including multi-directional Targeting CSC stemness-associated TME, inducing differentiation improve eradication and, therefore, treatment. This review comprehensively summarized these targeted therapies, along with their current status clinical trials. By exploring implementing strategies aimed at eradicating CSCs, researchers aim treatment outcomes overcome challenges posed by CSC-mediated therapy resistance.

Language: Английский

Citations

43
Neurodevelopmental disorders, like cancer, are connected to impaired chromatin remodelers, PI3K/mTOR, and PAK1-regulated MAPK DOI Creative Commons
Ruth Nussinov, Bengi Ruken Yavuz, M. Kaan Arici

et al.

Biophysical Reviews, Journal Year: 2023, Volume and Issue: 15(2), P. 163 - 181

Published: April 1, 2023

Neurodevelopmental disorders (NDDs) and cancer share proteins, pathways, mutations. Their clinical symptoms are different. However, individuals with NDDs have higher probabilities of eventually developing cancer. Here, we review the literature ask how shared features can lead to different medical conditions why having an NDD first increase chances malignancy. To explore these vital questions, focus on dysregulated PI3K/mTOR, a major brain cell growth pathway in differentiation, MAPK, critical proliferation, hallmark Differentiation is governed by chromatin organization, making aberrant remodelers highly likely agents NDDs. Dysregulated organization accessibility influence lineage specific types at embryonic development stages. PAK1, pivotal roles cancer, also regulates MAPK. We review, clarify, connect pathways proliferation differentiation highlight PAK1 role MAPK regulation. Exactly activation controls development, remodeler components, e.g., BAF170 encoded

Language: Английский

Citations

37
The Hippo Pathway Effectors YAP/TAZ-TEAD Oncoproteins as Emerging Therapeutic Targets in the Tumor Microenvironment DOI Open Access

Reza Bayat Mokhtari,

Neda Ashayeri,

Leili Baghaie

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(13), P. 3468 - 3468

Published: July 2, 2023

Various cancer cell-associated intrinsic and extrinsic inputs act on YAP/TAZ proteins to mediate the hyperactivation of TEAD transcription factor-based transcriptome. This YAP/TAZ-TEAD activity can override growth-limiting Hippo tumor-suppressor pathway that maintains normal tissue homeostasis. Herein, we provide an integrated summary contrasting roles during homeostasis versus tumor initiation progression. In addition upstream factors regulate in TME, critical insights emerging functions immune suppression abnormal vasculature development tumorigenesis are illustrated. Lastly, discuss current methods intervene with oncogenic signaling applications combination therapies, gut microbiota, epigenetic plasticity could potentiate efficacy chemo/immunotherapy as improved therapeutic strategies.

Language: Английский

Citations

34
Melodic maestros: Unraveling the role of miRNAs in the diagnosis, progression, and drug resistance of malignant pleural mesothelioma DOI

Mai A. Abd‐Elmawla,

Sherif S. Abdel Mageed, Tohada M. AL‐Noshokaty

et al.

Pathology - Research and Practice, Journal Year: 2023, Volume and Issue: 250, P. 154817 - 154817

Published: Sept. 13, 2023

Language: Английский

Citations

25
SIRT7 promotes Hippo/YAP activation and cancer cell proliferation in hepatocellular carcinoma via suppressing MST1 DOI Creative Commons

Yiying Gu,

Cong Ding,

Tingzi Yu

et al.

Cancer Science, Journal Year: 2024, Volume and Issue: 115(4), P. 1209 - 1223

Published: Jan. 30, 2024

Abstract Abnormal activation of the oncogene YAP in Hippo pathway is a major feature liver cancer and inactivation MST1/2 has been shown to be responsible for overactivation that led tumorigenesis. However, mechanisms underlying dysregulation remain poorly understood. RNA‐seq analysis genome (KEGG) enrichment were used identify genes pathways regulated by SIRT7. qRT‐PCR, ChIP, luciferase assay investigate transcriptional regulation. Mass spectrometry, co‐immunoprecipitation immunoprecipitation exam protein–protein interaction post‐transcriptional modification. A xenograft mouse model was confirm effect SIRT7 inhibitors on hepatocellular carcinoma (HCC) proliferation vivo. We found suppresses MST1 both regulation modification, which turn promotes nuclear localization cancer. Mechanistically, we revealed transcription binding promoter inducing H3K18 deacetylation its region. In addition, directly binds deacetylates MST1, primes acetylation‐dependent ubiquitination protein degradation. clinical samples, confirmed negative correlation between levels, high expression correlated with elevated localization. specific inhibitor 2800Z sufficiently inhibited HCC growth disrupting SIRT7/MST1/YAP axis. Our data thus previously undescribed function regulating further proved targeting might provide novel therapeutic options treatment

Language: Английский

Citations

17