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 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.

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 SPSB1, a Novel Negative Regulator of the Transforming Growth Factor-β Signaling Pathway Targeting the Type II Receptor

2015 ◽  
Vol 290 (29) ◽  
pp. 17894-17908 ◽  
Author(s):  
Sheng Liu ◽  
Thao Nheu ◽  
Rodney Luwor ◽  
Sandra E. Nicholson ◽  
Hong-Jian Zhu
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Negative Regulator ◽  
Type Ii

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.

scholarly journals Myostatin Signals through a Transforming Growth Factor β-Like Signaling Pathway To Block Adipogenesis

2003 ◽  
Vol 23 (20) ◽  
pp. 7230-7242 ◽  
Author(s):  
A. Rebbapragada ◽  
H. Benchabane ◽  
J. L. Wrana ◽  
A. J. Celeste ◽  
L. Attisano
Keyword(s):  
Signal Transduction ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Signal Transduction Pathway ◽  
Transforming Growth Factor Β ◽  
Negative Regulator ◽  
Type I ◽  
Type Ii ◽  
Transduction Pathway

ABSTRACT Myostatin, a transforming growth factor β (TGF-β) family member, is a potent negative regulator of skeletal muscle growth. In this study we characterized the myostatin signal transduction pathway and examined its effect on bone morphogenetic protein (BMP)-induced adipogenesis. While both BMP7 and BMP2 activated transcription from the BMP-responsive I-BRE-Lux reporter and induced adipogenic differentiation, myostatin inhibited BMP7- but not BMP2-mediated responses. To dissect the molecular mechanism of this antagonism, we characterized the myostatin signal transduction pathway. We showed that myostatin binds the type II Ser/Thr kinase receptor. ActRIIB, and then partners with a type I receptor, either activin receptor-like kinase 4 (ALK4 or ActRIB) or ALK5 (TβRI), to induce phosphorylation of Smad2/Smad3 and activate a TGF-β-like signaling pathway. We demonstrated that myostatin prevents BMP7 but not BMP2 binding to its receptors and that BMP7-induced heteromeric receptor complex formation is blocked by competition for the common type II receptor, ActRIIB. Thus, our results reveal a strikingly specific antagonism of BMP7-mediated processes by myostatin and suggest that myostatin is an important regulator of adipogenesis.

scholarly journals Role of the transforming growth factor‐β signaling pathway in the pathogenesis of colorectal cancer

2018 ◽  
Vol 120 (6) ◽  
pp. 8899-8907 ◽  
Author(s):  
Atena Soleimani ◽  
Mehran Pashirzad ◽  
Amir Avan ◽  
Gordon A. Ferns ◽  
Majid Khazaei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β

scholarly journals Axin Facilitates Smad3 Activation in the Transforming Growth Factor β Signaling Pathway

2001 ◽  
Vol 21 (15) ◽  
pp. 5132-5141 ◽  
Author(s):  
Masao Furuhashi ◽  
Ken Yagi ◽  
Hideki Yamamoto ◽  
Yoichi Furukawa ◽  
Shinji Shimada ◽  
...  
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Glycogen Synthase ◽  
Transforming Growth Factor Β ◽  
Receptor Activation ◽  
Negative Regulator ◽  
Type I ◽  
Ligand Stimulation

ABSTRACT Axin acts as a negative regulator in Wnt signaling through interaction with various molecules involved in this pathway, including β-catenin, adenomatous polyposis coli, and glycogen synthase kinase 3β. We show here that Axin also regulates the effects of Smad3 on the transforming growth factor β (TGF-β) signaling pathway. In the absence of activated TGF-β receptors. Axin physically interacted with Smad3 through its C-terminal region located between the β-catenin binding site and Dishevelled-homologous domain. An Axin homologue, Axil (also called conductin), also interacted with Smad3. In the absence of ligand stimulation, Axin was colocalized with Smad3 in the cytoplasm in vivo. Upon receptor activation, Smad3 was strongly phosphorylated by TGF-β type I receptor (TβR-I) in the presence of Axin, and dissociated from TβR-I and Axin. Moreover, the transcriptional activity of TGF-β was enhanced by Axin and repressed by an Axin mutant which is able to bind to Smad3. Axin may thus function as an adapter of Smad3, facilitating its activation by TGF-β receptors for efficient TGF-β signaling.

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