TGF-β – an excellent servant but a bad master

Abstract

The transforming growth factor (TGF-β) family of growth factors controls an immense number of cellular responses and figures prominently in development and homeostasis of most human tissues. Work over the past decades has revealed significant insight into the TGF-β signal transduction network, such as activation of serine/threonine receptors through ligand binding, activation of SMAD proteins through phosphorylation, regulation of target genes expression in association with DNA-binding partners and regulation of SMAD activity and degradation. Disruption of the TGF-β pathway has been implicated in many human diseases, including solid and hematopoietic tumors. As a potent inhibitor of cell proliferation, TGF-β acts as a tumor suppressor; however in tumor cells, TGF-β looses anti-proliferative response and become an oncogenic factor. This article reviews current understanding of TGF-β signaling and different mechanisms that lead to its impairment in various solid tumors and hematological malignancies.

Effect of malaria components on blood mononuclear cells involved in immune response

“…During malaria infection, increased plasma IL-10 has been reported in the serum of malaria patients on admission [43] and elevated IL-10 levels have been detected in serum of Thai patients with acute P. falciparum malaria prior to treatment, with normal levels returning after treatment [44] . Moreover, transforming growth factor (TGF)-β appeared to act as an immunosuppressant, contributing to inhibition of NF-κB activation [45] . TGF-β mRNA and protein were expressed in CM post-mortem brain tissue from Malawian children infected with P. falciparum malaria [46] .…”

Cilia and coordination of signaling networks during heart development

“…92 This network comprises a multitude of different ligand types that act through the activation of a family of transmembrane receptor serine/threonine kinases, which in part activate Smad transcription factors to elicit different cellular responses during development and in tissue homeostasis. 92,93 Nodal, Lefty1, and Lefty2 are all members of the TGFβ ligand superfamily. Like Shh, Nodal and Lefty1/2 are asymmetrically expressed in the node and involved in establishment of L-R asymmetry in the mouse embryo (see above, reviewed in ref.…”

Extramedullary relapse of multiple myeloma defined as the highest risk group based on deregulated gene expression data

“…On the other hand, TGF-β inhibits proliferation and immunoglobulin secretion of normal B-cells. Therefore, it is clear that regulation of TGF-β plays an important role in MM development and progression 25 . The TMPO gene is located on locus 12q22.…”