YAP/TAZ-associated cell signaling – at the crossroads of cancer and neurodevelopmental disorders

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 28, 2025

YAP/TAZ (Yes-associated protein/paralog transcriptional co-activator with PDZ-binding domain) are cofactors that the key and major downstream effectors of Hippo signaling pathway. Both known to play a crucial role in defining cellular outcomes, including cell differentiation, proliferation, apoptosis. Aside from canonical cascade components MST1/2 (mammalian STE20-like kinase 1/2), SAV1 (Salvador homologue 1), MOB1A/B (Mps one binder activator 1A/B) LATS1/2 (large tumor suppressor 1/2) upstream YAP/TAZ, activation is also influenced by numerous other pathways. Such non-canonical regulation includes well-known growth factor pathways such as epidermal receptor (EGFR)/ErbB family, Notch, Wnt well cell-cell adhesion, cell-matrix interactions mechanical cues cell’s microenvironment. This puts at center complex network capable regulating developmental processes tissue regeneration. On hand, dysregulation has been implicated diseases various cancers neurodevelopmental disorders. Indeed, recent years, parallels between cancer development disorders have become apparent being these review discusses brain development, special focus on interconnection different conditions.

Language: Английский

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Functional Tumor Boundaries Revealed by Dynamic Electroimpedance Imaging Under Weak Stimuli: Dissipative Structures in Melanoma Area

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 2, 2025

Abstract Real-time imaging and monitoring of tumor boundaries are critical for understanding growth dynamics ensuring precise treatment. All physiological phenomena, specifically communicational, inherently bioelectrical. Our original technology “Skin Electrodynamic Introscopy” (SEI) firstly enabled time-lapse skin spectral electroimpedance landscape (SEL) with an unprecedented combination temporal spatial resolution. SEI the revelation several new phenomena in collective dynamics: emergence dynamic SEL structures melanoma region response to weak short stimuli, such as ischemia non-thermal EMF MF. The main objective this work was identify criteria assessing functional a its peritumor ecosystem. These conceptualized dissipative (DS)—self-organizing patterns that arise nonequilibrium thermodynamic systems, malignant tumors serving striking example. It is shown impedance exceed optical dimensions can vary at different levels intra- intercellular environment. proposed quasi-stationary manifestation entropy/negentropy flow from tumor. boundary be assessed by revealing pre-bifurcation zone measuring increment stimulation resulting activation emitters. In context, invasive front detected appearance antiphase structure border. Thus, previously discovered well number ones, considered first demonstrations DS tissue cellular level. determined primarily increased group sensitivity/state cells their components, rather than individual elements. insight into test-induced behavior allows more nuanced (i.e. local system) metabolism compared traditional reductionist approaches. nature observed most effectively represented fluctuation correlation fields SEL, reflecting thus fundamental concept DS: ‘Order chaos’, which especially relevant biology. particular, demonstrated as: - Transition initially chaotic specific back upon cessation stimulus; Abrupt shift magnitude depth front; Manifestation stroma pre-existing nevus mitochondrial field; Emergence resistance influence systemic post-effect, etc; Moreover, difference images frames made it possible trace process form of: Wave-like around morphological tumor; Expansion initial microclusters boundary; Reverse migration towards negentropy From chaos’ perspective, similarity found between manifestations information (EMF) energy (ischemia) influence. Herewith we also attempted estimate content spatio-temporal version ion balance index (as ratio modulus 2 kHz 1 MHz). support hypothesis, supplement presents analysis two experiments: Papillomatous model exploring viral theory cancer), revealed similar complementary effects reorganization SEL; Plant (plant leaf), demonstrating universal phenomenon structuring. summary, melanoma, particularly context boundaries, reveals insights how progression. discovery represents significant advancement our developed approach highlights potential advanced techniques, it: facilitates real-time biofeedback laboratory clinical settings; need paradigm cancer research; challenge views on exposure induce biological responses level; calls investigating entities shaped interactions environmental factors, thereby opening up opportunities innovative treatment approaches target adaptive behavior.

Language: Английский

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Transcriptome-Wide Insights: Neonatal Lactose Intolerance Promotes Telomere Damage, Senescence, and Cardiomyopathy in Adult Rat Heart

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1584 - 1584

Published: Feb. 13, 2025

Cardiovascular diseases (CVD) are the primary cause of mortality globally. A significant aspect CVD involves their association with aging and susceptibility to neonatal programming. These factors suggest that adverse conditions during development can disrupt cardiomyocyte differentiation, thereby leading heart dysfunction. This study focuses on long-term effects inflammatory oxidative stress due lactose intolerance (NLI) transcriptome phenotype. Our recent bioinformatic focused toggle genes indicated NLI correlates switch off some in thyroid hormone, calcium, antioxidant signaling pathways, alongside switch-on/off involved DNA damage response inflammation. In presented study, we evaluated ploidy different regions left ventricle (LV), complemented by a transcriptomic analysis quantitative (gradual) difference expression. Cytophotometric morphologic analyses LV cardiomyocytes identified hyperpolyploidy bridges between nuclei suggesting telomere fusion. Transcriptomic profiling highlighted damage, aging, chromatin decompaction, along suppression pathways governing muscle contraction energy metabolism. Echocardiography revealed statistically dilation decrease ejection fraction. The estimation survival rates shortened median lifespan approximately 18% (p < 0.0001) compared control. Altogether, these findings may increase cardiovascular accelerating increased hyperpolyploidization reduced cardiac contractile function. Collectively, our data emphasize importance early identification management metabolic stressors, such as NLI, mitigate risks.

Language: Английский

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p21‐Activated Kinase 1 (Pak1) as an Element in Functional and Dysfunctional Interplay Among the Myocardium, Adipose Tissue, and Pancreatic Beta Cells

Comprehensive physiology, Journal Year: 2025, Volume and Issue: 15(2)

Published: March 10, 2025

This review focuses on p21-activated kinase 1 (Pak1), a multifunctional, highly conserved enzyme that regulates multiple downstream effectors present in many tissues. Upstream signaling via Ras-related small G-proteins, Cdc42/Rac1 promotes the activity of Pak1. Our hypothesis is this cascade an important element communication among myocardium, adipose tissue, and pancreatic β-cells. Evidence indicates shared property these tissues structure/function stability requires homeostatic Pak1 activity. Increases or decreases may promote dysfunction increase susceptibility to stressors. increased levels be protective provides support for efforts develop therapeutic approaches activating with potential use prevalent disorders associated obesity, diabetes, myocardial dysfunction. On other hand, since cancer progression, there has been significant effort inhibitors. These opposing highlight need deep understanding relation development effective selective therapies minimal absent off-target effects.

Language: Английский

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Research Progress in pathogenesis of connective tissue disease-associated interstitial lung disease from the perspective of pulmonary cells

Autoimmunity Reviews, Journal Year: 2024, Volume and Issue: 23(7-8), P. 103600 - 103600

Published: July 1, 2024

Language: Английский

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Interplay of Glucose Metabolism and Hippo Pathway in Chondrocytes: Pathophysiology and Therapeutic Targets

Bioengineering, Journal Year: 2024, Volume and Issue: 11(10), P. 972 - 972

Published: Sept. 27, 2024

In this review, we explore the intricate relationship between glucose metabolism and mechanotransduction pathways, with a specific focus on role of Hippo signaling pathway in chondrocyte pathophysiology. Glucose is vital element maintaining proper function, but it has also been implicated pathogenesis osteoarthritis (OA) via induction pro-inflammatory pathways establishment an intracellular environment conducive to OA. Alternatively, such as possess capacity respond mechanical stimuli have integral homeostasis. However, these can be dysregulated potentially contribute progression We discussed how alterations levels may modulate components variety mechanisms. Characterizing interaction highlights necessity balancing both metabolic maintain health optimal functionality. Furthermore, review demonstrates scarcity literature provides summary current research dedicated area study. Ultimately, increased into topic elucidate novel mechanisms relationships integrating metabolism. Through hope inspire future develop innovative treatments for addressing clinical challenges

Language: Английский

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YAP/TAZ Signalling Controls Epidermal Keratinocyte Fate

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12903 - 12903

Published: Nov. 30, 2024

The paralogues Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) control cell proliferation fate determination from embryogenesis to ageing. In the skin epidermis, these proteins are involved in both homeostatic renewal injury-induced regeneration also drive carcinogenesis other pathologies. YAP TAZ usually considered downstream of Hippo pathway. However, they central integrating link for signalling microenvironment since interplay cascades induced by growth factors, cytokines, physical parameters extracellular matrix. this review, we summarise evidence on how activated epidermal keratinocytes; YAP/TAZ-mediated cooperates molecules at plasma membrane, cytoplasmic, nuclear levels; YAP/TAZ ultimately controls transcription programmes, defining fate.

Language: Английский

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