From Quiescence to Activation: The Reciprocal Regulation of Ras and Rho Signaling in Hepatic Stellate Cells DOI Creative Commons

Saeideh Nakhaei‐Rad,

Silke Pudewell, Amin Mirzaiebadizi

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(9), P. 674 - 674

Published: May 5, 2025

Chronic liver diseases are marked by persistent inflammation and can evolve into fibrosis, cirrhosis, hepatocellular carcinoma. In an affected liver, hepatic stellate cells (HSCs) transition from a quiescent to activated state adopt myofibroblast-like cell phenotype. While these play role in supporting regeneration, they also have detrimental effects on function as the disease progresses fibrosis cirrhosis. These findings highlight dynamic switching between different signaling pathways involving Ras, Rho GTPases, Notch signaling. Notably, two specific members of Ras Eras Rnd3, predominantly expressed HSCs, while Mras Rhoc more abundant their forms. addition, this study highlights critical cytosolic Notch1 HSCs Rock HSCs. We hypothesize that distinct yet interdependent intracellular networks regulate HSC fate decisions key ways: maintaining quiescence homeostasis facilitating activation, thereby influencing processes such proliferation, transdifferentiation, mesenchymal transition. The proposed model, combined with methodological tools for state, will deepen our understanding mechanisms underlying chronic may pave way innovative therapies. therapies could include small molecule drugs targeting Ras- Rho-dependent pathways.

Language: Английский

[Research Advances in Targeting the YAP/TAZ Signaling Pathway 
to Improve Cancer Immunotherapy]. DOI

Pingxu Zhang,

Yiyi Zhan

PubMed, Journal Year: 2025, Volume and Issue: 28(3), P. 221 - 229

Published: March 20, 2025

Despite the groundbreaking advances in cancer immunotherapy achieved by immune checkpoint inhibitors (ICIs), their efficacy remains limited immunosuppressive tumor microenvironment (TME). Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), key effectors of Hippo signaling pathway, play pivotal roles evasion. They directly regulate expression checkpoints, mediate formation an microenvironment, inhibit T cell function, interact other pathways to promote escape. Diverse strategies targeting YAP/TAZ have been developed, including direct inhibition, modulation upstream regulators, suppression downstream target genes. Preclinical studies demonstrated that combining inhibition ICIs significantly enhances therapeutic across various models. This review summarizes recent understanding role evasion within TME explores potential this pathway improve outcomes. Furthermore, it discusses translational value combination therapies based on providing a theoretical framework practical guidance for development innovative immunotherapeutic precision medicine approaches. .

Language: Английский

Citations

0
From Quiescence to Activation: The Reciprocal Regulation of Ras and Rho Signaling in Hepatic Stellate Cells DOI Creative Commons

Saeideh Nakhaei‐Rad,

Silke Pudewell, Amin Mirzaiebadizi

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(9), P. 674 - 674

Published: May 5, 2025

Chronic liver diseases are marked by persistent inflammation and can evolve into fibrosis, cirrhosis, hepatocellular carcinoma. In an affected liver, hepatic stellate cells (HSCs) transition from a quiescent to activated state adopt myofibroblast-like cell phenotype. While these play role in supporting regeneration, they also have detrimental effects on function as the disease progresses fibrosis cirrhosis. These findings highlight dynamic switching between different signaling pathways involving Ras, Rho GTPases, Notch signaling. Notably, two specific members of Ras Eras Rnd3, predominantly expressed HSCs, while Mras Rhoc more abundant their forms. addition, this study highlights critical cytosolic Notch1 HSCs Rock HSCs. We hypothesize that distinct yet interdependent intracellular networks regulate HSC fate decisions key ways: maintaining quiescence homeostasis facilitating activation, thereby influencing processes such proliferation, transdifferentiation, mesenchymal transition. The proposed model, combined with methodological tools for state, will deepen our understanding mechanisms underlying chronic may pave way innovative therapies. therapies could include small molecule drugs targeting Ras- Rho-dependent pathways.

Language: Английский

Citations

0