The Interactivity between TGFβ and BMP Signaling in Organogenesis, Fibrosis, and Cancer

The Transforming Growth Factor beta (TGFβ) and Bone Morphogenic Protein (BMP) pathways intersect at multiple signaling hubs and cooperatively or counteractively participate to bring about cellular processes which are critical not only for tissue morphogenesis and organogenesis during development, but also for adult tissue homeostasis. The proper functioning of the TGFβ/BMP pathway depends on its communication with other signaling pathways and any deregulation leads to developmental defects or diseases, including fibrosis and cancer. In this review we explore the cellular and physio-pathological contexts in which the synergism or antagonism between the TGFβ and BMP pathways are crucial determinants for the normal developmental processes, as well as the progression of fibrosis and malignancies.

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The Role of TGF-β Signaling Regulatory MicroRNAs in the Pathogenesis of Colorectal Cancer

Current Pharmaceutical Design ◽

10.2174/1381612825666190110150705 ◽

2019 ◽

Vol 24 (39) ◽

pp. 4611-4618 ◽

Cited By ~ 9

Author(s):

Reyhaneh Moradi-Marjaneh ◽

Majid Khazaei ◽

Gordon A. Ferns ◽

Seyed H. Aghaee-Bakhtiari

Keyword(s):

Colorectal Cancer ◽

Signaling Pathway ◽

Transforming Growth Factor Beta ◽

Molecular Mechanisms ◽

Transforming Growth Factor ◽

Growth Factor Beta ◽

And Migration ◽

Multiple Signaling ◽

Tgf Β1

Colorectal cancer (CRC) is one of the most common cancers globally and is associated with a high mortality rate. The transforming growth factor beta (TGF-β) signaling pathway plays an important role in normal intestinal tissue function, but has also been implicated in the development of CRC. MicroRNAs (miRNAs) have also recently emerged as important regulators of cancer development and progression. They act by targeting multiple signaling pathways including the TGF-β signaling pathway. There is growing evidence demonstrating that miRNAs target various components of the TGF-β signaling pathway, including TGF-β1, TGF-β2, regulatory SMADs (SMAD1, 2, 3, 5 and 9), co-mediator SMAD4, inhibitory SMADs (SMAD6 and 7) and the TGF-β receptors, and thereby alter the proliferation and migration of CRC cells. In this review, we summarize the data concerning the interaction between TGF-β signaling pathway and miRNAs with the aim to better understanding the CRC molecular mechanisms and hence better management of this disease.

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Feedback regulation of BMP signaling by Caenorhabditis elegans cuticle collagens

Molecular Biology of the Cell ◽

10.1091/mbc.e19-07-0390 ◽

2020 ◽

Vol 31 (8) ◽

pp. 825-832 ◽

Cited By ~ 1

Author(s):

Uday Madaan ◽

Lionel Faure ◽

Albar Chowdhury ◽

Shahrear Ahmed ◽

Emma J. Ciccarelli ◽

...

Keyword(s):

Extracellular Matrix ◽

Caenorhabditis Elegans ◽

Growth Factor ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Feedback Regulation ◽

Bmp Signaling ◽

Reciprocal Interactions ◽

Growth Factor Beta ◽

Cuticle Collagens

Transforming growth factor beta (TGF-β) and related signals can be regulated by the extracellular matrix (ECM). We identify a novel contact-independent regulation of DBL-1 TGF-β/BMP–related signaling by collagens in Caenorhabditis elegans. These collagens are transcriptional targets of the pathway, indicating reciprocal interactions between DBL-1 signaling and the ECM.

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ALMS1 Regulates TGF-β Signaling and Morphology of Primary Cilia

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.623829 ◽

2021 ◽

Vol 9 ◽

Author(s):

María Álvarez-Satta ◽

Mauro Lago-Docampo ◽

Brais Bea-Mascato ◽

Carlos Solarat ◽

Sheila Castro-Sánchez ◽

...

Keyword(s):

Growth Factor ◽

Cell Line ◽

Transforming Growth Factor Beta ◽

Primary Cilia ◽

Transforming Growth Factor ◽

Cellular Signaling ◽

Bmp Signaling ◽

Morphogenetic Protein ◽

Growth Factor Beta

In this study, we aimed to evaluate the role of ALMS1 in the morphology of primary cilia and regulation of cellular signaling using a knockdown model of the hTERT-RPE1 cell line. ALMS1 depletion resulted in the formation of longer cilia, which often displayed altered morphology as evidenced by extensive twisting and bending of the axoneme. Transforming growth factor beta/bone morphogenetic protein (TGF-β/BMP) signaling, which is regulated by primary cilia, was similarly affected by ALMS1 depletion as judged by reduced levels of TGFβ-1-mediated activation of SMAD2/3. These results provide novel information on the role of ALMS1 in the function of primary cilia and processing of cellular signaling, which when aberrantly regulated may underlie Alström syndrome.

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Extracellular BMP Antagonists, Multifaceted Orchestrators in the Tumor and Its Microenvironment

International Journal of Molecular Sciences ◽

10.3390/ijms21113888 ◽

2020 ◽

Vol 21 (11) ◽

pp. 3888

Author(s):

Sarah Ouahoud ◽

James C.H. Hardwick ◽

Lukas J.A.C. Hawinkels

Keyword(s):

Cancer Progression ◽

Bone Morphogenetic Proteins ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Bmp Signaling ◽

Biological Processes ◽

Adult Tissue ◽

Aberrant Expression ◽

Bmp Pathway ◽

Bmp Antagonists

The bone morphogenetic proteins (BMPs), a subgroup of the transforming growth factor-β (TGF-β) superfamily, are involved in multiple biological processes such as embryonic development and maintenance of adult tissue homeostasis. The importance of a functional BMP pathway is underlined by various diseases, including cancer, which can arise as a consequence of dysregulated BMP signaling. Mutations in crucial elements of this signaling pathway, such as receptors, have been reported to disrupt BMP signaling. Next to that, aberrant expression of BMP antagonists could also contribute to abrogated signaling. In this review we set out to highlight how BMP antagonists affect not only the cancer cells, but also the other cells present in the microenvironment to influence cancer progression.

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The Balance between Acetylation and Deacetylation Controls Smad7 Stability

Journal of Biological Chemistry ◽

10.1074/jbc.m503134200 ◽

2005 ◽

Vol 280 (23) ◽

pp. 21797-21803 ◽

Cited By ~ 110

Author(s):

Maria Simonsson ◽

Carl-Henrik Heldin ◽

Johan Ericsson ◽

Eva Grönroos

Keyword(s):

Growth Factor ◽

Transforming Growth Factor Beta ◽

Histone Deacetylases ◽

Transforming Growth Factor ◽

Cellular Proteins ◽

General Mechanism ◽

Cellular Processes ◽

Lysine Residues ◽

Growth Factor Beta ◽

The Stability

Transforming growth factor beta (TGFβ) regulates multiple cellular processes via activation of Smad signaling pathways. We have recently demonstrated that the inhibitory Smad7 interacts with the acetyl transferase p300 and that p300 acetylates Smad7 on two lysine residues. These lysine residues are critical for Smurf-mediated ubiquitination of Smad7, and acetylation protects Smad7 from TGFβ-induced degradation. In this study we demonstrate that Smad7 interacts with specific histone deacetylases (HDACs) and that the same HDACs are able to deacetylate Smad7. The interaction with HDACs is dependent on the C-terminal MH2 domain of Smad7. In addition, HDAC1-mediated deacetylation of Smad7 decreases the stability of Smad7 by enhancing its ubiquitination. Thus, our results demonstrate that the degradation of Smad7 is regulated by the balance between acetylation, deacetylation and ubiquitination, indicating that this could be a general mechanism to regulate the stability of cellular proteins.

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