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

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.

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Role of transforming growth factor-β in hematologic malignancies

Blood ◽

10.1182/blood-2005-10-4169 ◽

2006 ◽

Vol 107 (12) ◽

pp. 4589-4596 ◽

Cited By ~ 154

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.

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Transforming growth factor-β and myostatin signaling in skeletal muscle

Journal of Applied Physiology ◽

10.1152/japplphysiol.01091.2007 ◽

2008 ◽

Vol 104 (3) ◽

pp. 579-587 ◽

Cited By ~ 182

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.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00022-07 ◽

2007 ◽

Vol 51 (8) ◽

pp. 2905-2910 ◽

Cited By ~ 29

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.

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