USP1 modulates hepatocellular carcinoma progression via the Hippo/TAZ axis DOI Creative Commons
Dongyi Liu,

Quanhui Li,

Yifeng Zang

и другие.

Cell Death and Disease, Год журнала: 2023, Номер 14(4)

Опубликована: Апрель 12, 2023

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. The Hippo signaling pathway has emerged as a significant suppressive for hepatocellular carcinogenesis. core components constitute kinase cascade, which inhibits functional activation YAP/TAZ. Interestingly, overactivation YAP/TAZ commonly observed in carcinoma, although inhibitory cascade still functional. Recent studies have indicated that ubiquitin‒proteasome system also plays important roles modulating activity. Our DUB (deubiquitinase) siRNA screen showed USP1 critical regulator Analysis TCGA data demonstrated expression elevated HCC and associated with poor survival patients. RNA sequencing analysis revealed depletion affects activity cell lines. Mechanistic assays required Hippo/TAZ axis progression. interacted WW domain TAZ, subsequently enhanced TAZ stability by suppressing K11-linked polyubiquitination TAZ. study identifies novel mechanism linking regulating possible therapeutic target HCC.

Язык: Английский

The Hippo signalling pathway and its implications in human health and diseases DOI Creative Commons

Minyang Fu,

Yuan Hu,

Tianxia Lan

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Ноя. 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.

Язык: Английский

Процитировано

347
Mechanical regulation of chromatin and transcription DOI
Sirio Dupont, Sara A. Wickström

Nature Reviews Genetics, Год журнала: 2022, Номер 23(10), С. 624 - 643

Опубликована: Май 23, 2022

Язык: Английский

Процитировано

148
Control of stem cell renewal and fate by YAP and TAZ DOI
Jordan H. Driskill, Duojia Pan

Nature Reviews Molecular Cell Biology, Год журнала: 2023, Номер 24(12), С. 895 - 911

Опубликована: Авг. 25, 2023

Язык: Английский

Процитировано

74
Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics DOI Creative Commons
Xiao Ma, Tengda Huang, Xi Chen

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Фев. 8, 2025

Язык: Английский

Процитировано

7
ROS-induced cytosolic release of mitochondrial PGAM5 promotes colorectal cancer progression by interacting with MST3 DOI Creative Commons
Shiyang Wang, Xi Wu,

Wenxin Bi

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 6, 2025

Aberrant release of mitochondrial reactive oxygen species (mtROS) in response to cellular stress is well known for promoting cancer progression. However, precise molecular mechanism by which mtROS contribute epithelial progression remains only partially understood. Here, using colorectal (CRC) models, we show that upon sensing excessive mtROS, phosphatase PGAM5, normally localizes the mitochondria, undergoes aberrant cleavage presenilin-associated rhomboid-like protein (PARL), becoming released into cytoplasm. Cytosolic PGAM5 then directly binds and dephosphorylates MST3 kinase. This, turn, prevents STK25-mediated LATS1/2 phosphorylation, leading YAP activation CRC Importantly, depletion reciprocally promotes accumulation cytosolic inducing damage. Taken together, these findings demonstrate how activating via a post-transcriptional positive feedback loop between MST3, both can serve as potential targets developing next-generation anti-colon therapeutics. Dysregulation contributes intestinal tumorigenesis. Here authors report induces cytoplasm subsequent dephosphorylation kinase,

Язык: Английский

Процитировано

4
Decellularized extracellular matrix mediates tissue construction and regeneration DOI Creative Commons
Chuanqi Liu, Ming Pei, Qingfeng Li

и другие.

Frontiers of Medicine, Год журнала: 2021, Номер 16(1), С. 56 - 82

Опубликована: Дек. 28, 2021

Contributing to organ formation and tissue regeneration, extracellular matrix (ECM) constituents provide with three-dimensional (3D) structural integrity cellular-function regulation. Containing the crucial traits of cellular microenvironment, ECM substitutes mediate cell-matrix interactions prompt stem-cell proliferation differentiation for 3D organoid construction in vitro or regeneration vivo. However, these ECMs are often applied generically have yet be extensively developed specific cell types cultures. Cultured cells also produce rich ECM, particularly stromal cells. Cellular improves culture development remodeling during wound healing after implantation into host as well. Gaining better insight derived from either that regulate reconstruction helps us select, produce, implant most suitable thus promote vivo regeneration. Overall, decellularization methodologies tissue/cell-derived scaffolds cellular-growth supplements used propagation discussed. Moreover, current preclinical applications by which components modulate wound-healing process reviewed.

Язык: Английский

Процитировано

94
Stem cell therapy in liver regeneration: Focus on mesenchymal stem cells and induced pluripotent stem cells DOI
Lu Zhang,

Xiao-Jing-Nan Ma,

Yuan-Yuan Fei

и другие.

Pharmacology & Therapeutics, Год журнала: 2021, Номер 232, С. 108004 - 108004

Опубликована: Сен. 28, 2021

Язык: Английский

Процитировано

66
Extra- and Intra-Cellular Mechanisms of Hepatic Stellate Cell Activation DOI Creative Commons
Yufei Yan,

Jiefei Zeng,

Linhao Xing

и другие.

Biomedicines, Год журнала: 2021, Номер 9(8), С. 1014 - 1014

Опубликована: Авг. 14, 2021

Hepatic fibrosis is characterized by the pathological accumulation of extracellular matrix (ECM) in liver resulting from persistent injury and wound-healing reaction induced various insults. Although hepatic considered reversible after eliminating cause injury, chronic left unchecked can progress to cirrhosis cancer. A better understanding cellular molecular mechanisms controlling fibrotic response needed develop novel clinical strategies. It well documented that activated stellate cells (HSCs) most principal players promoting synthesis deposition ECM components. In current review, we discuss pathways HSC activation, emphasizing emerging extra- intra-cellular signals drive this important fibrosis. number cell types external stimuli converge upon HSCs promote their including hepatocytes, sinusoidal endothelial cells, macrophages, cytokines, altered ECM, hepatitis viral infection, enteric dysbiosis, lipid metabolism disorder, exosomes, microRNAs, alcohol, drugs parasites. We also signaling intracellular events individually or synergistically TGFβ/Smad, Notch, Wnt/β-catenin, Hedgehog Hippo pathways. These findings will provide potential therapeutic targets arrest reverse cirrhosis.

Язык: Английский

Процитировано

64
Hippo signaling pathway and respiratory diseases DOI Creative Commons
Weifeng Tang, Min Li,

Xiaoting Yangzhong

и другие.

Cell Death Discovery, Год журнала: 2022, Номер 8(1)

Опубликована: Апрель 20, 2022

The hippo signaling pathway is a highly conserved evolutionary that plays an important role in regulating cell proliferation, organ size, tissue development, and regeneration. Increasing evidences consider the involved process of respiratory diseases. Hippo mainly composed mammalian STE20-like kinase 1/2 (MST1/2), large tumor suppressor (LATS1/2), WW domain Sav family containing protein 1 (SAV1), MOB activator (MOB1), Yes-associated (YAP) or transcriptional coactivator with PDZ-binding motif (TAZ), members TEA (TEAD) family. YAP cascade effector pathway. activation promotes pulmonary arterial vascular smooth muscle cells (PAVSMCs) which leads to remodeling; thereby hypertension (PAH) aggravated. While loss high expression inflammatory genes accumulation cells, pneumonia consequently exacerbated. In addition, overexpressed proliferation lung fibroblasts collagen deposition; idiopathic fibrosis (IPF) promoted. Moreover, knockout reduces deposition senescence adult alveolar epithelial (AECs); hence IPF slowed. may be repair acute injury (ALI) by promoting differentiation progenitor intervening capillary endothelium. asthma. conclusion, More researches are needed focus on molecular mechanisms participates

Язык: Английский

Процитировано

45
The m6A methyltransferase Mettl3 deficiency attenuates hepatic stellate cell activation and liver fibrosis DOI Creative Commons

Yanli Li,

Xinmei Kang, Zhuowei Zhou

и другие.

Molecular Therapy, Год журнала: 2022, Номер 30(12), С. 3714 - 3728

Опубликована: Авг. 3, 2022

Activation of hepatic stellate cells (HSCs) is a central driver liver fibrosis. Previous investigations have identified various altered epigenetic landscapes during the cellular progression HSC activation. N6-methyladenosine (m6A) most abundant internal RNA modification in eukaryotic and dynamically regulated under physiological pathophysiological conditions. However, functional role Mettl3-mediated m6A fibrosis remains elusive. Here, we found that HSC-specific knockout methyltransferase Mettl3 suppressed activation significantly alleviated Multi-omics analysis HSCs showed depletion reduced deposition on mRNA transcripts Lats2 (a player Hippo/YAP signaling pathway) slowed down their degradation. Elevated increased phosphorylation downstream transcription factor YAP, YAP nuclear translocation, decreased pro-fibrotic gene expression. Overexpressing mutant resistant to by partially rescued expression Mettl3-deficient HSCs. Our study revealed disruption mitigated controlling pathway, providing potential therapeutic strategies alleviate targeting epitranscriptomic machinery.

Язык: Английский

Процитировано

43