The Hippo signaling pathway in development and regeneration

Zhong, Zhenxing; Jiao, Zhihan; Yu, Fa-Xing

doi:10.1016/j.celrep.2024.113926

Cited by 12 publications

(2 citation statements)

References 195 publications

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“…Expression in Other Cell-Types: Hippo signaling pathway, originally recognized for its involvement in regulating organ size and tissue growth, is fundamental for the development and maintenance of various cell types beyond hepatocytes. In epithelial cells, the Hippo pathway governs processes such as proliferation, differentiation, and polarity [259]. Across different tissues like the skin, intestine, and lung, Hippo signaling orchestrates…”

Section: Hippo Signaling Pathwaymentioning

confidence: 99%

Mapping Heterogeneity of Hepatocellular Carcinoma by Investigating Hepatocyte-Specific Genes/TFs/Pathways Across Cellular and Tumor Landscapes

Shafi,

Rajpar,

Zafar

et al. 2024

Preprint

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Background: Hepatocellular carcinoma (HCC) presents challenges due to tumor heterogeneity and therapeutic resistance. Understanding the molecular mechanisms driving heterogeneity is crucial. Key transcription factors (HNF4A, HNF1A, FOXA1/2, etc.) and signaling pathways (Wnt/β-catenin, FGF, HGF, etc.) are dysregulated in HCC. Dysregulation disrupts hepatocyte genetic programming, leading to heterogeneous cell populations. Investigating these mechanisms offers insights for targeted therapies and improving patient outcomes in HCC. Methods: Databases, including PubMed, MEDLINE, Google Scholar, and open access/ subscription-based journals were searched for published articles without any date restrictions, to trace the emergence of HCC heterogeneity by investigating the hepatocyte-specific genes/TFs/signaling pathways across cellular and tumor landscapes. Based on the criteria mentioned in the methods section, studies were systematically reviewed to investigate HCC Heterogeneity. This study adheres to relevant PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Results: This study into hepatocellular carcinoma (HCC) revealed dysregulation of key transcription factors (TFs) and signaling pathways. Transcription factors HNF4A, HNF1A, FOXA1/2, CEBPA, GATA4/6, PROX1, SOX9, HNF6/Onecut1, and ONECUT2/HNF6β showed altered expression patterns, disrupting hepatocyte genetic programming and promoting heterogeneous cell populations in HCC. Dysregulated Wnt/β-catenin, FGF, HGF, TGF-β, and Hippo signaling pathways influenced cellular fate decisions and interactions with the tumor microenvironment, further contributing to HCC heterogeneity. Dysregulated NOTCH signaling and TBX3/18 transcription factors highlighted the complexity of HCC heterogeneity. This study points to the critical role of dysregulated TFs and signaling pathways in driving HCC heterogeneity and transdifferentiation, providing insights for targeted therapeutic interventions to improve patient outcomes. Conclusion: The decline in the gene expression of hepatocyte cell type-specific genes dysregulates the genetic programing of hepatocytes involved in cell type-specific homeostasis. The multiple roles of every gene/TF begin to manifest themselves causing the emergence of heterogeneity. The dysregulation of hepatocyte-specific genes and signaling pathways in hepatocellular carcinoma (HCC) disrupts cellular homeostasis, leading to the emergence of heterogeneity and transdifferentiation. Key transcription factors like HNF4A, HNF1A, and FOXA1/2, along with pathways such as Wnt/β-catenin and Hippo signaling, play crucial roles. This disruption sets the stage for diverse cellular phenotypes within the tumor microenvironment. Understanding these molecular mechanisms is vital for developing targeted therapeutic strategies to address HCC heterogeneity and improve patient outcomes.

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Section: Hippo Signaling Pathwaymentioning

confidence: 99%

Mapping Heterogeneity of Hepatocellular Carcinoma by Investigating Hepatocyte-Specific Genes/TFs/Pathways Across Cellular and Tumor Landscapes

Shafi,

Rajpar,

Zafar

et al. 2024

Preprint

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“…NAFLD is a pro-inflammatory disorder characterized by liver fibrosis, which alters tissue stiffness that can potentially activate mechanosensing pathways such as the Hippo pathway [10,11]. Among other roles, the Hippo pathway has been shown to regulate cell survival, proliferation, migration and differentiation [12]. Yes-associated protein (YAP) and Transcriptional co-Activator with PDZ-binding motif (TAZ) [13] are key Hippo pathway transcriptional co-activators that are mobilized from the cytosol to the nucleus where they interact when unphosphorylated with the transcriptional enhanced associate domain (TEAD) transcription factors [14].…”

Section: Introductionmentioning

confidence: 99%

The role of YAP/TAZ signaling in dendritic cell-mediated pathogenesis of insulin resistance and non-alcoholic fatty liver disease

Schcolnik-Cabrera,

Lee,

Dzierlega

et al. 2024

Preprint

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Obesity and insulin resistance (IR) are global health challenges linked to metabolic diseases, such as type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). High-caloric intake, which is associated to NAFLD, induces adipocyte hypertrophy and inflammation, triggering dendritic cell (DC) activation and systemic inflammation. DC exacerbate inflammation by promoting pro-inflammatory responses, aggravating IR and NAFLD progression. NAFLD is characterized by liver fibrosis, which alters tissue stiffness that can trigger mechanosensing pathways such as the Hippo pathway in immune cell types. In this work we explored the roles of key mediators of the Hippo pathway, YAP and TAZ, in DCs within the context of liver fibrosis, obesity and IR, using a model of NAFLD induced by feeding a high fat high sucrose diet. Our findings indicate that specific deletion of YAP and/or TAZ in DCs had minimal impact on IR development and metabolic tissue inflammation. We conclude that YAP and TAZ have limited and possibly redundant roles in the immune pathophysiology of NAFLD and IR.

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Angiomotin family proteins in the Hippo signaling pathway

Wang,

2024

BioEssays

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The Motin family proteins (Motins) are a class of scaffolding proteins consisting of Angiomotin (AMOT), AMOT‐like protein 1 (AMOTL1), and AMOT‐like protein 2 (AMOTL2). Motins play a pivotal role in angiogenesis, tumorigenesis, and neurogenesis by modulating multiple cellular signaling pathways. Recent findings indicate that Motins are components of the Hippo pathway, a signaling cascade involved in development and cancer. This review discusses how Motins are integrated into the Hippo signaling network, as either upstream regulators or downstream effectors, to modulate cell proliferation and migration. The repression of YAP/TAZ by Motins contributes to growth inhibition, whereas subcellular localization of Motins and their interactions with actin fibers are critical in regulating cell migration. The net effect of Motins on cell proliferation and migration may contribute to their diverse biological functions.

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The Hippo signaling pathway in development and regeneration

Cited by 12 publications

References 195 publications

Mapping Heterogeneity of Hepatocellular Carcinoma by Investigating Hepatocyte-Specific Genes/TFs/Pathways Across Cellular and Tumor Landscapes

Mapping Heterogeneity of Hepatocellular Carcinoma by Investigating Hepatocyte-Specific Genes/TFs/Pathways Across Cellular and Tumor Landscapes

The role of YAP/TAZ signaling in dendritic cell-mediated pathogenesis of insulin resistance and non-alcoholic fatty liver disease

Angiomotin family proteins in the Hippo signaling pathway

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