During the course of breast cancer progression, normally dormant tumour-promoting effects of transforming growth factor b (TGFb), including migration, invasion, and metastasis are unmasked. In an effort to identify mechanisms that regulate the pro-migratory TGFb ‘switch’ in mammary epithelial cells in vitro, we found that TGFb stimulates the phosphorylation of Smad1 and Smad5, which are typical...

Tissue homeostasis in mammals relies on powerful cytostatic and differentiation signals delivered by the cytokine TGFb and relayed within the cell via the activation of Smad transcription factors. Formation of transcription regulatory complexes by the association of Smad4 with receptor-phosphorylated Smads 2 and 3 is a central event in the canonical TGFb pathway. Here we provide evidence for a ...

Elevated levels of TGFb are a negative prognostic indicator for patients diagnosed with pancreatic cancer; as a result, the TGFb pathway is an attractive target for therapy. However, clinical application of pharmacologic inhibition of TGFb remains challenging because TGFb has tumor suppressor functions in many epithelial malignancies, including pancreatic cancer. In fact, direct neutralization ...

Advanced tumors produce an excessive amount of transforming growth factor b (TGFb), which promotes tumor progression at late stages of malignancy. The purpose of this study was to develop anti-TGFb therapeutics for cancer. We synthesized a novel small-molecule TGFb receptor I kinase (activin receptor– like kinase 5) inhibitor termedN-[[4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2...

This study investigated the combined application of Transforming Growth Factor b-1 (TGFb-1) and Bone Morphogenetic Protein-2 (BMP-2) to stimulate osteogenic expression in vitro. TGFb-1 and BMP-2 fulfill specific roles in the formation of new bone. COLLOSS E, a bone-derived collagen product containing a variety of naturally occurring growth factors, was also used. Growth factors were administere...

The TGFb-mediated alteration of the tumor microenvironment plays a crucial role in tumor progression. Mesothelial cells are the primary components of the tumor microenvironment for ovarian cancer cells; however, the exact role of TGFb-stimulatedmesothelial cells in ovarian cancer progression remains uncertain. In this report, we examined the effects of TGFb-treated mesothelial cells on ovarian ...

BACKGROUND & AIMS Pancreatic stellate cells (PSCs) regulate the development of chronic pancreatitis (CP) and are activated by the cytokine transforming growth factor β (TGFB). Integrins of the αv family promote TGFB signaling in mice, probably by interacting with the Arg-Gly-Asp (RGD) sequence of the TGFB latency-associated peptide, which frees TGFB to bind its cellular receptors. However, litt...