scholarly journals The TGF-β Family: Signaling Pathways, Developmental Roles, and Tumor Suppressor Activities

2002 ◽  
Vol 2 ◽  
pp. 892-925 ◽  
Author(s):  
Aaron N. Johnson ◽  
Stuart J. Newfeld
Keyword(s):  
Tumor Suppressor ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Family Members ◽  
Transforming Growth Factor Β ◽  
Suppressor Activity ◽  
Wide Range ◽  
Tumor Suppressor Activity ◽  
Multicellular Organisms

Intercellular communication is a critical process for all multicellular organisms, and communication among cells is required for proper embryonic development and adult physiology. Members of the Transforming Growth Factor-β (TGF-β) family of secreted proteins communicate information between cells via a complex signaling pathway, and family members are capable of inducing a wide range of cellular responses. The purpose of this review is to provide the reader with a broad introduction to our current understanding of three aspects of the TGF-β family. These are the molecular mechanisms utilized by TGF-β signaling pathways, the developmental roles played by TGF-β family members in a variety of species, and the growing list of cancers in which various TGF-β signaling pathways display tumor suppressor activity.

scholarly journals Advances in the Development Ubiquitin-Specific Peptidase (USP) Inhibitors

2021 ◽  
Vol 22 (9) ◽  
pp. 4546
Author(s):  
Shiyao Chen ◽  
Yunqi Liu ◽  
Huchen Zhou
Keyword(s):  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Regulatory System ◽  
Transforming Growth Factor Β ◽  
Molecular Signaling ◽  
Post Translational Modification ◽  
The Past ◽  
Damage Repair ◽  
Wide Range ◽  
Cancer And Inflammation

Ubiquitylation and deubiquitylation are reversible protein post-translational modification (PTM) processes involving the regulation of protein degradation under physiological conditions. Loss of balance in this regulatory system can lead to a wide range of diseases, such as cancer and inflammation. As the main members of the deubiquitinases (DUBs) family, ubiquitin-specific peptidases (USPs) are closely related to biological processes through a variety of molecular signaling pathways, including DNA damage repair, p53 and transforming growth factor-β (TGF-β) pathways. Over the past decade, increasing attention has been drawn to USPs as potential targets for the development of therapeutics across diverse therapeutic areas. In this review, we summarize the crucial roles of USPs in different signaling pathways and focus on advances in the development of USP inhibitors, as well as the methods of screening and identifying USP inhibitors.

scholarly journals The Molecular Mechanism of Epithelial–Mesenchymal Transition for Breast Carcinogenesis

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 476 ◽  
Author(s):  
Chia-Jung Li ◽  
Pei-Yi Chu ◽  
Giou-Teng Yiang ◽  
Meng-Yu Wu
Keyword(s):  
Epithelial Cells ◽  
Tumor Progression ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Transforming Growth Factor Β ◽  
Inhibition Of Proliferation ◽  
Mesenchymal Transition

The transforming growth factor-β (TGF-β) signaling pathway plays multiple regulatory roles in the tumorigenesis and development of cancer. TGF-β can inhibit the growth and proliferation of epithelial cells and induce apoptosis, thereby playing a role in inhibiting breast cancer. Therefore, the loss of response in epithelial cells that leads to the inhibition of cell proliferation due to TGF-β is a landmark event in tumorigenesis. As tumors progress, TGF-β can promote tumor cell invasion, metastasis, and drug resistance. At present, the above-mentioned role of TGF-β is related to the interaction of multiple signaling pathways in the cell, which can attenuate or abolish the inhibition of proliferation and apoptosis-promoting effects of TGF-β and enhance its promotion of tumor progression. This article focuses on the molecular mechanisms through which TGF-β interacts with multiple intracellular signaling pathways in tumor progression and the effects of these interactions on tumorigenesis.

scholarly journals Simvastatin and ROCK Inhibitor Y-27632 Inhibit Myofibroblast Differentiation of Graves’ Ophthalmopathy-Derived Orbital Fibroblasts via RhoA-Mediated ERK and p38 Signaling Pathways

2021 ◽  
Vol 11 ◽  
Author(s):  
Yi-Hsuan Wei ◽  
Shu-Lang Liao ◽  
Sen-Hsu Wang ◽  
Chia-Chun Wang ◽  
Chang-Hao Yang
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Transforming Growth Factor Β ◽  
Mapk Signaling ◽  
Myofibroblast Differentiation ◽  
Rock Inhibitor ◽  
Graves Ophthalmopathy ◽  
Orbital Fibroblasts

Transforming growth factor-β (TGF-β)-induced differentiation of orbital fibroblasts into myofibroblasts is an important pathogenesis of Graves’ ophthalmopathy (GO) and leads to orbital tissue fibrosis. In the present study, we explored the antifibrotic effects of simvastatin and ROCK inhibitor Y-27632 in primary cultured GO orbital fibroblasts and tried to explain the molecular mechanisms behind these effects. Both simvastatin and Y-27632 inhibited TGF-β-induced α-smooth muscle actin (α-SMA) expression, which serves as a marker of fibrosis. The inhibitory effect of simvastatin on TGF-β-induced RhoA, ROCK1, and α-SMA expression could be reversed by geranylgeranyl pyrophosphate, an intermediate in the biosynthesis of cholesterol. This suggested that the mechanism of simvastatin-mediated antifibrotic effects may involve RhoA/ROCK signaling. Furthermore, simvastatin and Y-27632 suppressed TGF-β-induced phosphorylation of ERK and p38. The TGF-β-mediated α-SMA expression was suppressed by pharmacological inhibitors of p38 and ERK. These results suggested that simvastatin inhibits TGF-β-induced myofibroblast differentiation via suppression of the RhoA/ROCK/ERK and p38 MAPK signaling pathways. Thus, our study provides evidence that simvastatin and ROCK inhibitors may be potential therapeutic drugs for the prevention and treatment of orbital fibrosis in GO.

An emerging role for the nuclear localization of maspin in the suppression of tumor progression and metastasis1This article is part of Special Issue entitled Asilomar Chromatin and has undergone the Journal’s usual peer review process.

2012 ◽  
Vol 90 (1) ◽  
pp. 22-38 ◽  
Author(s):  
Brigitte Goulet ◽  
Gabriel Chan ◽  
Ann F. Chambers ◽  
John D. Lewis
Keyword(s):  
Tumor Suppressor ◽  
Nuclear Localization ◽  
Molecular Mechanisms ◽  
Additional Data ◽  
Mammary Epithelial Cells ◽  
Peer Review Process ◽  
Mammary Epithelial ◽  
Suppressor Activity ◽  
Tumor Suppressor Activity ◽  
Normal Mammary Epithelial

Maspin, a member of the serpin family of serine protease inhibitors, was originally identified as a tumor suppressor that is expressed in normal mammary epithelial cells but is reduced or absent in breast carcinomas. Early enthusiasm for maspin as a biomarker for disease progression has been tempered by clinical data that associates maspin with favourable outcomes in some studies and poor prognosis in others. Here, we review all of the published clinical studies for maspin in breast and ovarian cancers and propose that the apparent discordance between clinical reports is a consequence of differential cellular distribution of maspin. Indeed, it was thought that an extracellular pool of maspin possessed tumor suppressor activity, acting by inhibiting migration and increasing cell adhesion. Recent evidence from our group and others indicates, however, that the nuclear localization of maspin in cancer cells is necessary for its tumor suppressor activity. We provide additional data here to demonstrate that nuclear-localized maspin binds to chromatin and is required to effectively prevent cells from metastasizing. Our knowledge of other serpins that localize to the nucleus should help to inform future studies of nuclear maspin. Elucidation of the molecular mechanisms regulating the localization and activities of maspin should pave the way for the development of improved diagnostics and therapies for cancer.

scholarly journals TGFβ family signaling and development

Development ◽  
2021 ◽  
Vol 148 (5) ◽  
Author(s):  
Shunji Jia ◽  
Anming Meng
Keyword(s):  
Signal Transduction ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Family Members ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Dorsoventral Patterning ◽  
Tgfβ Signaling ◽  
Evolutionarily Conserved ◽  
Transduction Mechanisms

ABSTRACT The transforming growth factor β (TGFβ) signaling family is evolutionarily conserved in metazoans. The signal transduction mechanisms of TGFβ family members have been expansively investigated and are well understood. During development and homeostasis, numerous TGFβ family members are expressed in various cell types with temporally changing levels, playing diverse roles in embryonic development, adult tissue homeostasis and human diseases by regulating cell proliferation, differentiation, adhesion, migration and apoptosis. Here, we discuss the molecular mechanisms underlying signal transduction and regulation of the TGFβ subfamily pathways, and then highlight their key functions in mesendoderm induction, dorsoventral patterning and laterality development, as well as in the formation of several representative tissues/organs.

scholarly journals Signaling pathways involved in colorectal cancer progression

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Zahra Koveitypour ◽  
Farnoush Panahi ◽  
Mehrdad Vakilian ◽  
Maryam Peymani ◽  
Farzad Seyed Forootan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Growth Factor Receptor ◽  
Transforming Growth Factor Β ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Cascades

AbstractColorectal cancer (CRC) is the fourth leading cause of the worldwide cancer mortality. Different molecular mechanisms have been attributed to the development and progress of CRC. In this review, we will focus on the mitogen-activated protein kinase (MAPK) cascades downstream of the epidermal growth factor receptor (EGFR), Notch, PI3K/AKT pathway, transforming growth factor-β (TGF-β), and Wnt signaling pathways. Various mutations in the components of these signaling pathways have been linked to the development of CRC. Accordingly, numerous efforts have been carried out to target the signaling pathways to develop novel therapeutic approaches. Herein, we review the signaling pathways involved in the incidence and progression of CRC, and the strategies for the therapy targeting components of signaling pathways in CRC.

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