The JAK/STAT signaling pathway: from bench to clinic

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Nov. 26, 2021

Abstract The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway was discovered more than a quarter-century ago. As fulcrum many vital cellular processes, the JAK/STAT constitutes rapid membrane-to-nucleus module induces expression various critical mediators cancer inflammation. Growing evidence suggests that dysregulation is associated with cancers autoimmune diseases. In this review, we discuss current knowledge about composition, activation, regulation pathway. Moreover, highlight role its inhibitors in

Language: Английский

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Targeting TGF-β Signaling in Cancer

Trends in cancer, Journal Year: 2017, Volume and Issue: 3(1), P. 56 - 71

Published: Jan. 1, 2017

Language: Английский

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Cellular signalling by primary cilia in development, organ function and disease

Nature Reviews Nephrology, Journal Year: 2019, Volume and Issue: 15(4), P. 199 - 219

Published: Feb. 7, 2019

Language: Английский

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Notch signaling pathway: architecture, disease, and therapeutics

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: March 24, 2022

Abstract The NOTCH gene was identified approximately 110 years ago. Classical studies have revealed that signaling is an evolutionarily conserved pathway. receptors undergo three cleavages and translocate into the nucleus to regulate transcription of target genes. deeply participates in development homeostasis multiple tissues organs, aberration which results cancerous noncancerous diseases. However, recent indicate outcomes are changeable highly dependent on context. In terms cancers, can both promote inhibit tumor various types cancer. overall performance NOTCH-targeted therapies clinical trials has failed meet expectations. Additionally, mutation been proposed as a predictive biomarker for immune checkpoint blockade therapy many cancers. Collectively, pathway needs be integrally assessed with new perspectives inspire discoveries applications. this review, we focus classical latest findings related illustrate history, architecture, regulatory mechanisms, contributions physiological development, diseases, therapeutic applications microenvironment cancer immunotherapy also highlighted. We hope review will help not only beginners but experts systematically thoroughly understand

Language: Английский

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Specificity, versatility, and control of TGF-β family signaling

Science Signaling, Journal Year: 2019, Volume and Issue: 12(570)

Published: Feb. 26, 2019

Encoded in mammalian cells by 33 genes, the transforming growth factor-β (TGF-β) family of secreted, homodimeric and heterodimeric proteins controls differentiation most, if not all, cell lineages many aspects tissue physiology multicellular eukaryotes. Deregulation TGF-β signaling leads to developmental anomalies disease, whereas enhanced contributes cancer fibrosis. Here, we review fundamentals mechanisms that are initiated upon ligand binding its surface receptors dependence responses on input from cooperation with other pathways. We discuss how exquisitely control functional presentation activation heteromeric receptor complexes transmembrane, dual-specificity kinases and, thus, define their context-dependent responsiveness ligands. also introduce through which called Smads act as intracellular effectors ligand-induced gene expression show specificity impressive versatility Smad depend cross-talk Last, non-Smad mechanisms, distinct ligand-activated complexes, complement thus contribute cellular responses.

Language: Английский

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TGF-β Signaling

Biomolecules, Journal Year: 2020, Volume and Issue: 10(3), P. 487 - 487

Published: March 23, 2020

Transforming growth factor-β (TGF-β) represents an evolutionarily conserved family of secreted polypeptide factors that regulate many aspects physiological embryogenesis and adult tissue homeostasis. The TGF-β members are also involved in pathophysiological mechanisms underlie diseases. Although the comprises factors, which exhibit cell type-specific developmental stage-dependent biological actions, they all signal via signaling pathways. controlled at extracellular level, where ligand secretion, deposition to matrix activation prior play important roles. At plasma membrane TGF-βs associate with receptor kinases mediate phosphorylation-dependent downstream mediators, mainly SMAD proteins, oligomerization-dependent ubiquitin ligases intracellular protein kinases. interplay between SMADs other proteins regulatory signals control expression target genes, RNA processing multiple levels, mRNA translation nuclear or cytoplasmic regulation. This article emphasizes importance biochemical executing functions by prototype member family, TGF-β.

Language: Английский

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A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering

Bone and Joint Research, Journal Year: 2018, Volume and Issue: 7(3), P. 232 - 243

Published: March 1, 2018

Despite its intrinsic ability to regenerate form and function after injury, bone tissue can be challenged by a multitude of pathological conditions. While innovative approaches have helped unravel the cascades healing, this knowledge has so far not improved clinical outcomes defect treatment. Recent findings allowed us gain in-depth about physiological conditions biological principles regeneration. Now it is time transfer lessons learned from healing challenging scenarios in defects employ technologies enable biomaterial-based strategies for healing. This review aims provide an overview on endogenous material formation how these are transferred new perspectives biomaterial-driven Cite article: T. Winkler, F. A. Sass, G. N. Duda, K. Schmidt-Bleek. A biomaterials remaining shortcomings future opportunities engineering: The unsolved challenge. Bone Joint Res 2018;7:232–243. DOI: 10.1302/2046-3758.73.BJR-2017-0270.R1.

Language: Английский

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TGF-β1 – A truly transforming growth factor in fibrosis and immunity

Seminars in Cell and Developmental Biology, Journal Year: 2019, Volume and Issue: 101, P. 123 - 139

Published: Dec. 24, 2019

Language: Английский

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Pathophysiological communication between hepatocytes and non-parenchymal cells in liver injury from NAFLD to liver fibrosis

Advanced Drug Delivery Reviews, Journal Year: 2021, Volume and Issue: 176, P. 113869 - 113869

Published: July 16, 2021

Language: Английский

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TGF-β Family Signaling in Mesenchymal Differentiation

Cold Spring Harbor Perspectives in Biology, Journal Year: 2017, Volume and Issue: 10(5), P. a022202 - a022202

Published: May 15, 2017

Mesenchymal stem cells (MSCs) can differentiate into several lineages during development and also contribute to tissue homeostasis regeneration, although the requirements for both may be distinct. MSC lineage commitment progression in differentiation are regulated by members of transforming growth factor-β (TGF-β) family. This review focuses on roles TGF-β family signaling mesenchymal osteoblasts, chondrocytes, myoblasts, adipocytes, tenocytes. We summarize reported findings cell culture studies, animal models, interactions with other pathways highlight how aberrations drive human disease affecting differentiation.

Language: Английский

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