Marfan syndrome (MFS) is an autosomal dominant disorder of connective tissue, caused by mutations of the microfibrillar protein fibrillin-1, that predisposes affected individuals to aortic aneurysm and rupture and is associated with increased TGFβ signaling. TGFβ is secreted from cells as a latent complex consisting of TGFβ, the TGFβ propeptide, and a molecule of latent TGFβ binding protein (LT...

The transforming growth factor-β (TGFβ) is a potent regulator of tumorigenesis. In cancer, two distinctive behaviors of TGFβ have been reported as a tumor suppressor at early stage of the disease, and as a tumor promoter at later stages. The past decades, the dualistic role of TGFβ has garnered a lot of attention. As a result, cancer researchers' has been tasked to elucidate how TGFβ signaling ...

Members of the transforming growth factor β (TGFβ) family initiate cellular responses by binding to TGFβ receptor type II (TβRII) and type I (TβRI) serine/threonine kinases, whereby Smad2 and Smad3 are phosphorylated and activated, promoting their association with Smad4. We report here that TβRI interacts with the SH3 domains of the adaptor protein CIN85 in response to TGFβ stimulation in a TRA...

Leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5), an intestinal stem cell marker, is known to exhibit tumor suppressor activity in colon cancer, the mechanism of which is not understood. Here we show that R-spondin 1 (RSPO1)/LGR5 directly activates TGFβ signaling cooperatively with TGFβ type II receptor in colon cancer cells, enhancing TGFβ-mediated growth inhibition and stres...

The members of the transforming growth factor beta (TGFβ) family of cytokines, including bone morphogenetic proteins (BMP), play fundamental roles in development and tissue homeostasis. Hence, aberrant TGFβ/BMP signalling is associated with several human diseases such as fibrosis, bone and immune disorders, cancer progression and metastasis. Consequently, targeting TGFβ signalling for intervent...

The predominantly tumorigenic actions of transforming growth factor-beta (TGFβ) in aggressive cancer make the TGFβ pathway an attractive target for therapeutic intervention. Currently a number of TGFβ-targeted cancer therapies are in clinical trials. However, due to the multifaceted role of TGFβ signaling, antagonizing TGFβ in the clinical setting is challenging. Therefore it is essential to de...

Transforming growth factor-β (TGFβ) promotes glomerular hypertrophy and matrix expansion, leading to glomerulosclerosis. MicroRNAs are well suited to promote fibrosis because they can repress gene expression, which negatively regulate the fibrotic process. Recent cellular and animal studies have revealed enhanced expression of microRNA, miR-21, in renal cells in response to TGFβ. Specific miR-2...

Uterine carcinosarcomas (UCS) are rare (3-4%) but highly aggressive, accounting for a disproportionately high (16.4%) mortality among uterine malignancies. Transforming growth factor beta (TGFβ) is a multifunctional cytokine that regulates important cellular processes including epithelial-mesenchymal transition (EMT). Existence of biphasic elements and a report demonstrating amplification of TG...

Transforming growth factor-β (TGFβ) is a key mediator of fibrogenesis. TGFβ is overexpressed and activated in fibrotic diseases, regulates fibroblast differentiation into myofibroblasts and induces extracellular matrix deposition. Platelet-derived growth factor (PDGF) is also a regulator of fibrogenesis. Some studies showed a link between TGFβ and PDGF in certain fibrotic diseases. TGFβ induces...

Regulatory T-cells (Tregs) are an inherent suppressive cell of the immune system with an established developmental requirement for the cytokine transforming growth factor β (TGFβ). However, the precise mechanisms by which mature Tregs utilize TGFβ during disease are unclear. In the May issue of Immunity, we have demonstrated that effector regulatory T-cells are essential activators of latent-TG...