In this study, we attempt to gain insights into the molecular mechanism underlying MDM2-mediated TGF-β resistance. MDM2 renders cells refractory to TGF-β by overcoming a TGF-β-induced G1 cell cycle arrest. Because the TGF-β resistant phenotype is reversible upon removal of MDM2, MDM2 likely confers TGF-β resistance by directly targeting the cellular machinery involved in the growth inhibition b...

Transforming growth factor-β (TGF-β) has roles in embryonic development, the prevention of inappropriate inflammation and tumour suppression. However, TGF-β signalling also regulates pathological epithelial-to-mesenchymal transition (EMT), inducing or progressing a number of diseases ranging from inflammatory disorders, to fibrosis and cancer. However, TGF-β signalling does not proceed linearly...

The TGF-β pathway is under active consideration as a cancer drug target based on its capacity to promote cancer cell invasion and to create a protumorigenic microenvironment. However, the clinical application of TGF-β inhibitors remains uncertain as genetic studies show a tumor suppressor function of TGF-β in pancreatic cancer and other epithelial malignancies. Here, we used genetically enginee...

In the majority of microsatellite-stable colorectal cancers (CRCs), an initiating mutation occurs in the adenomatous polyposis coli (APC) or β-catenin gene, activating the β-catenin/TCF pathway. The progression of resulting adenomas is associated with oncogenic activation of KRas and inactivation of the p53 and TGF-β/Smad functions. Most established CRC cell lines contain mutations in the TGF-β...

TGF-β is a ubiquitous cytokine that plays an active role in many cellular processes. Nearly every cell type has the ability to secrete TGF-β, as well as the ability to respond to TGF-β via the presence of TGF-β receptors on the cell surface. Consequently, gain or loss of function of the TGF-β pathway and its components are known to lead to a variety of diseases, including cancer. In epithelial ...

Transforming growth factor (TGF-β)/TGF-β receptor signal is known to promote cell migration. Up-regulation of TGF-β in serum/peritoneal fluid and increased levels of pluripotent transcription factor OCT4 in endometriotic tissues are frequently observed in patients with endometriosis. However, the mechanisms underlying how TGF-β/TGF-β receptor and OCT4 affect endometriotic cell migration still r...

Idiopathic pulmonary fibrosis (IPF) is a destructive disease in part resulting from premature or mature cellular aging. Protease-activated receptor-1 (PAR-1) recently emerged as a critical component in the context of fibrotic lung diseases. Therefore, we aimed to study the role of macrophages in PAR-1-mediated idiopathic pulmonary fibrosis. The number of macrophages were significantly reduced i...

Members of the transforming growth factor-β (TGF-β) family of secreted proteins are present in all multicellular animals. TGF-β proteins are versatile intercellular signalling molecules that orchestrate cell fate decisions during development and maintain homeostasis in adults. The Smad family of signal transducers implements TGF-β signals in responsive cells. Given the ability of TGF-β ligands ...