scholarly journals Transforming Growth Factor-Beta (TGFβ) Signaling Pathway in Cholangiocarcinoma

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 960 ◽  
Author(s):  
Panagiotis Papoutsoglou ◽  
Corentin Louis ◽  
Cédric Coulouarn
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Tgfβ Signaling ◽  
Efficient Treatment ◽  
Tumor Onset ◽  
Tgfβ Signaling Pathway

Cholangiocarcinoma is a deadly cancer worldwide, associated with a poor prognosis and limited therapeutic options. Although cholangiocarcinoma accounts for less than 15% of liver primary cancer, its silent nature restricts early diagnosis and prevents efficient treatment. Therefore, it is of clinical relevance to better understand the molecular basis of cholangiocarcinoma, including the signaling pathways that contribute to tumor onset and progression. In this review, we discuss the genetic, molecular, and environmental factors that promote cholangiocarcinoma, emphasizing the role of the transforming growth factor β (TGFβ) signaling pathway in the progression of this cancer. We provide an overview of the physiological functions of TGFβ signaling in preserving liver homeostasis and describe how advanced cholangiocarcinoma benefits from the tumor-promoting effects of TGFβ. Moreover, we report the importance of noncoding RNAs as effector molecules downstream of TGFβ during cholangiocarcinoma progression, and conclude by highlighting the need for identifying novel and clinically relevant biomarkers for a better management of patients with cholangiocarcinoma.

scholarly journals Structural biology of the TGFβ family

2019 ◽  
Vol 244 (17) ◽  
pp. 1530-1546 ◽  
Author(s):  
Erich J Goebel ◽  
Kaitlin N Hart ◽  
Jason C McCoy ◽  
Thomas B Thompson
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Structural Biology ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Biological Processes ◽  
Tgfβ Signaling ◽  
Growth Factor Beta ◽  
Tgfβ Signaling Pathway

The transforming growth factor beta (TGFβ) signaling pathway orchestrates a wide breadth of biological processes, ranging from bone development to reproduction. Given this, there has been a surge of interest from the drug development industry to modulate the pathway – at several points. This review discusses and provides additional context for several layers of the TGFβ signaling pathway from a structural biology viewpoint. The combination of structural techniques coupled with biophysical studies has provided a foundational knowledge of the molecular mechanisms governing this high impact, ubiquitous pathway, underlying many of the current therapeutic pursuits. This work seeks to consolidate TGFβ-related structural knowledge and educate other researchers of the apparent gaps that still prove elusive. We aim to highlight the importance of these structures and provide the contextual information to understand the contribution to the field, with the hope of advancing the discussion and exploration of the TGFβ signaling pathway. Impact statement The transforming growth factor beta (TGFβ) signaling pathway is a multifacetted and highly regulated pathway, forming the underpinnings of a large range of biological processes. Here, we review and consolidate the key steps in TGFβ signaling using literature rooted in structural and biophysical techniques, with a focus on molecular mechanisms and gaps in knowledge. From extracellular regulation to ligand–receptor interactions and intracellular activation cascades, we hope to provide an introductory base for understanding the TGFβ pathway as a whole.

scholarly journals Role of transforming growth factor-β in hematologic malignancies

Blood ◽  
2006 ◽  
Vol 107 (12) ◽  
pp. 4589-4596 ◽  
Author(s):  
Mei Dong ◽  
Gerard C. Blobe
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Myeloproliferative Disorders ◽  
Transforming Growth Factor Β ◽  
Hematologic Malignancies ◽  
Negative Regulator ◽  
Cellular Processes ◽  
Signaling Field

AbstractThe transforming growth factor-β (TGF-β) signaling pathway is an essential regulator of cellular processes, including proliferation, differentiation, migration, and cell survival. During hematopoiesis, the TGF-β signaling pathway is a potent negative regulator of proliferation while stimulating differentiation and apoptosis when appropriate. In hematologic malignancies, including leukemias, myeloproliferative disorders, lymphomas, and multiple myeloma, resistance to these homeostatic effects of TGF-β develops. Mechanisms for this resistance include mutation or deletion of members of the TGF-β signaling pathway and disruption of the pathway by oncoproteins. These alterations define a tumor suppressor role for the TGF-β pathway in human hematologic malignancies. On the other hand, elevated levels of TGF-β can promote myelofibrosis and the pathogenesis of some hematologic malignancies through their effects on the stroma and immune system. Advances in the TGF-β signaling field should enable targeting of the TGF-β signaling pathway for the treatment of hematologic malignancies.

scholarly journals Axolotl as a Model to Study Scarless Wound Healing in Vertebrates: Role of the Transforming Growth Factor Beta Signaling Pathway

2013 ◽  
Vol 2 (5) ◽  
pp. 250-260 ◽  
Author(s):  
Jean-François Denis ◽  
Mathieu Lévesque ◽  
Simon D. Tran ◽  
Aldo-Joseph Camarda ◽  
Stéphane Roy
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Growth Factor Beta

Transforming growth factor-β and myostatin signaling in skeletal muscle

2008 ◽  
Vol 104 (3) ◽  
pp. 579-587 ◽  
Author(s):  
Helen D. Kollias ◽  
John C. McDermott
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Muscle Development ◽  
Cellular Proliferation ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Related Family ◽  
Cytokine Milieu

The superfamily of transforming growth factor-β (TGF-β) cytokines has been shown to have profound effects on cellular proliferation, differentiation, and growth. Recently, there have been major advances in our understanding of the signaling pathway(s) conveying TGF-β signals to the nucleus to ultimately control gene expression. One tissue that is potently influenced by TGF-β superfamily signaling is skeletal muscle. Skeletal muscle ontogeny and postnatal physiology have proven to be exquisitely sensitive to the TGF-β superfamily cytokine milieu in various animal systems from mice to humans. Recently, major strides have been made in understanding the role of TGF-β and its closely related family member, myostatin, in these processes. In this overview, we will review recent advances in our understanding of the TGF-β and myostatin signaling pathways and, in particular, focus on the implications of this signaling pathway for skeletal muscle development, physiology, and pathology.

scholarly journals SB-431542, a Transforming Growth Factor β Inhibitor, Impairs Trypanosoma cruzi Infection in Cardiomyocytes and Parasite Cycle Completion

2007 ◽  
Vol 51 (8) ◽  
pp. 2905-2910 ◽  
Author(s):  
Mariana C. Waghabi ◽  
Michelle Keramidas ◽  
Claudia M. Calvet ◽  
Marcos Meuser ◽  
Maria de Nazaré C. Soeiro ◽  
...  
Keyword(s):  
Growth Factor ◽  
Trypanosoma Cruzi ◽  
Signaling Pathway ◽  
Chagas Disease ◽  
Transforming Growth Factor ◽  
Parasitic Infection ◽  
Transforming Growth Factor Β ◽  
Type I ◽  
Cruzi Infection

ABSTRACT The antiinflammatory cytokine transforming growth factor β (TGF-β) plays an important role in Chagas disease, a parasitic infection caused by the protozoan Trypanosoma cruzi. In the present study, we show that SB-431542, an inhibitor of the TGF-β type I receptor (ALK5), inhibits T. cruzi-induced activation of the TGF-β pathway in epithelial cells and in cardiomyocytes. Further, we demonstrate that addition of SB-431542 greatly reduces cardiomyocyte invasion by T. cruzi. Finally, SB-431542 treatment significantly reduces the number of parasites per infected cell and trypomastigote differentiation and release. Taken together, these data further confirm the major role of the TGF-β signaling pathway in both T. cruzi infection and T. cruzi cell cycle completion. Our present data demonstrate that small inhibitors of the TGF-β signaling pathway might be potential pharmacological tools for the treatment of Chagas disease.

Role of Transforming Growth Factor Beta in Human Cancer

2005 ◽  
Vol 23 (9) ◽  
pp. 2078-2093 ◽  
Author(s):  
Rebecca L. Elliott ◽  
Gerard C. Blobe
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Stromal Cells ◽  
Transforming Growth Factor ◽  
Human Cancer ◽  
Inhibition Of Proliferation ◽  
Human Cancers ◽  
Growth Factor Beta

Transforming growth factor beta (TGF-β) is a ubiquitous and essential regulator of cellular and physiologic processes including proliferation, differentiation, migration, cell survival, angiogenesis, and immunosurveillance. Alterations in the TGF-β signaling pathway, including mutation or deletion of members of the signaling pathway and resistance to TGF-β-mediated inhibition of proliferation are frequently observed in human cancers. Although these alterations define a tumor suppressor role for the TGF-β pathway in human cancer, TGF-β also mediates tumor-promoting effects, either through differential effects on tumor and stromal cells or through a fundamental alteration in the TGF-β responsiveness of the tumor cells themselves. TGF-β and members of the TGF-β signaling pathway are being evaluated as prognostic or predictive markers for cancer patients. Ongoing advances in understanding the TGF-β signaling pathway will enable targeting of this pathway for the chemoprevention and treatment of human cancers.

scholarly journals Transforming Growth Factor – β and Glioma

2020 ◽  
Vol 4 (3) ◽  
pp. 156
Author(s):  
Harrison Handoko ◽  
Novi Silvia Hardiany
Keyword(s):  
Growth Factor ◽  
Tumor Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Malignant Gliomas ◽  
Transforming Growth Factor Β ◽  
Genetic Mutation ◽  
Apoptosis Regulation ◽  
Lower Expression

Transforming growth factor-beta (TGF-β) is a regulatory cytokine secreted by various types of cell such as stromal cell, immune cells and tumor cells. Signaling of TGF-β plays an important role in proliferation, differentiation and apoptosis regulation of various cell, including glial cell. Disruption in the signaling pathway of TGF-β is commonly seen in tumor cells and is believed to contribute to the initiation and progression of cancer cells. Changes in the chromosome accompanied by genetic mutation has been observed which causes TGF-β to act as an oncogene, a substance which promote normal cells to differentiate to cancer cells.Increased level expression of TGF-β molecules has been seen in more malignant gliomas which yields a lower prognosis for the patient compared to those with lower expression of TGF-β. Malignant gliomas are characterized by rapid proliferation, invasion of parenchyma and angiogenic capabilities, are most common type of primary brain tumors. Studies have now implemented specific targeted therapy which act as a treatment for glioma cases. This review will focus on the role of TGF-β in glioma and its application in the treatment of glioma.International Journal of Human and Health Sciences Vol. 04 No. 03 July’20 Page : 156-160

scholarly journals Toward Regulatory Effects of Curcumin on Transforming Growth Factor-Beta Across Different Diseases: A Review

2020 ◽  
Vol 11 ◽  
Author(s):  
Milad Ashrafizadeh ◽  
Ali Zarrabi ◽  
Kiavash Hushmandi ◽  
Vahideh Zarrin ◽  
Ebrahim Rahmani Moghadam ◽  
...  
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Mitogen Activated Protein Kinase ◽  
Molecular Signaling ◽  
Cellular Events ◽  
Mitogen Activated Protein ◽  
Regulatory Effects

Immune response, proliferation, migration and angiogenesis are juts a few of cellular events that are regulated by transforming growth factor-β (TGF-β) in cells. A number of studies have documented that TGF-β undergoes abnormal expression in different diseases, e.g., diabetes, cancer, fibrosis, asthma, arthritis, among others. This has led to great fascination into this signaling pathway and developing agents with modulatory impact on TGF-β. Curcumin, a natural-based compound, is obtained from rhizome and roots of turmeric plant. It has a number of pharmacological activities including antioxidant, anti-inflammatory, anti-tumor, anti-diabetes and so on. Noteworthy, it has been demonstrated that curcumin affects different molecular signaling pathways such as Wnt/β-catenin, Nrf2, AMPK, mitogen-activated protein kinase and so on. In the present review, we evaluate the potential of curcumin in regulation of TGF-β signaling pathway to corelate it with therapeutic impacts of curcumin. By modulation of TGF-β (both upregulation and down-regulation), curcumin ameliorates fibrosis, neurological disorders, liver disease, diabetes and asthma. Besides, curcumin targets TGF-β signaling pathway which is capable of suppressing proliferation of tumor cells and invading cancer cells.

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