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TGF Beta Signaling and Its Role in Glioma Pathogenesis

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Glioma Signaling

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 986))

Abstract

Transforming growth factor beta (TGF-β) signaling is involved in the regulation of proliferation, differentiation and survival/or apoptosis of many cells, including glioma cells. TGF-β acts via specific receptors activating multiple intracellular pathways resulting in phosphorylation of receptor-regulated Smad2/3 proteins that associate with the common mediator, Smad4. Such complex translocates to the nucleus, binds to DNA and regulates transcription of many genes. Furthermore, TGF-β-activated kinase-1 (TAK1) is a component of TGF-β signaling and activates mitogen-activated protein kinase cascades. Negative regulation of TGF-β/Smad signaling may occur through the inhibitory Smad6/7. Increased expression of TGF-β1-3 correlates with a degree of malignancy of human gliomas. TGF-β may contribute to tumor pathogenesis by direct support of tumor growth, self-renewal of glioma initiating stem cells and inhibiting of anti-tumor immunity. TGF-β1,2 stimulate expression of the vascular endothelial growth factor as well as the plasminogen activator inhibitor and some metalloproteinases that are involved in vascular remodeling, angiogenesis and degradation of the extracellular matrix. Inhibitors of TGF-β signaling reduce viability and invasion of gliomas in animal models and show promises as novel, potential anti-tumor therapeutics.

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Abbreviations

ADAMTS-1:

Metalloproteinase and disintegrin-like domain

Akt:

Protein kinase B/Akt kinase

ALKs:

Activin-receptor-like kinases

AP-1:

Activator protein

BMPs:

Bone morphogenetic proteins

CTLs:

Cytotoxic T lymphocytes

EGFR:

Epidermal growth factor receptor

ECM:

Extracellular matrix

ERK1/2:

Extracellular signal-regulated kinases 1/2

GDFs:

Growth and differentiation factors

JAK:

Janus kinase

JNK c:

Jun N-terminal kinases

LAP:

Latency-associated peptide

LIF:

Leukemia inhibitory factor

LTBP:

Latent TGF-β binding protein

MT1-MMP:

Membrane-type 1 matrix metalloproteinase

p38 MAPK:

P38 mitogen-activated protein kinases

R-Smads:

Receptor-Smad proteins

SARA:

Smad anchor for receptor activation, STAT, signal transducer and activator of transcription

TAK1:

TGF-β-activated kinase-1

TβRI:

TGF-β type I receptor

TβRII:

TGF-β type II receptor

TGF-β:

Transforming growth factor β

TMZ:

Temozolomide

TNFα:

Tumor necrosis factor α

TRAF:

TNF receptor associated factor

VEGF:

Vascular endothelial growth factor.

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Acknowledgments

The work in the Author’s Laboratory is supported by a grant NN301 786240 from the Ministry of Science and Higher Education. M.K. is a recipient of a scholarship from Postgraduate School of Molecular Medicine.

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Authors and Affiliations

  1. Laboratory of Transcription Regulation, Department of Cell Biology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., PL 02-093, Warsaw, Poland

    Bozena Kaminska, Marta Kocyk & Magdalena Kijewska

  2. Postgraduate School of Molecular Medicine, Warsaw Medical University, Warsaw, Poland

    Marta Kocyk

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  1. Bozena Kaminska
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  2. Marta Kocyk
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  3. Magdalena Kijewska
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Correspondence to Bozena Kaminska .

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  1. , Biochemistry, Nencki Institute of Experimental Biology, Pasteur 3, Warsaw, 02-093, Poland

    Jolanta Barańska

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Kaminska, B., Kocyk, M., Kijewska, M. (2013). TGF Beta Signaling and Its Role in Glioma Pathogenesis. In: Barańska, J. (eds) Glioma Signaling. Advances in Experimental Medicine and Biology, vol 986. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4719-7_9

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