Transforming growth factor-beta (TGF-beta) family members exert their function via specific type I and type II serine/threonine kinase receptors and intracellular Smad transcription factors, including the common mediator Smad4. The dual effects of TGF-beta signaling on tumor initiation and progression are cell-specific and yet to be determined under distinct contexts. A number of genetically ma...

BACKGROUND Salivary gland tumors (SGTs) are known for their specific heterogeneity and ambiguous outcome for the affected patients. The LKB1 and SMAD4 genes are pivotal components of important signaling pathways, including AMPK and TGF-β. To our knowledge, no study has reported an association between the expression levels of these genes in SGTs. The expression levels of LKB1 and SMAD4 were eval...

The SMAD4 (DPC4) gene was initially isolated as a candidate tumor suppressor from the convergent site of homozygous deletions on 18q in a panel of pancreatic carcinoma cell lines. It encodes a common cytoplasmic signaling molecule shared by the transforming growth factor-beta, activin, and bone morphogenic pathways. We recently inactivated its mouse homologue Smad4 and demonstrated its role in ...

Although transforming growth factor-beta (TGF-beta) is both a suppressor and promoter of tumorigenesis, its contribution to early tumor suppression and staging remains largely unknown. In search of the mechanism of early tumor suppression, we identified the adaptor protein ELF, a beta-spectrin from stem/progenitor cells committed to foregut lineage. ELF activates and modulates Smad4 activation ...

The Ski family of nuclear oncoproteins represses TGF-beta signaling through interactions with the Smad proteins. The crystal structure of the Smad4 binding domain of human c-Ski in complex with the MH2 domain of Smad4 reveals specific recognition of the Smad4 L3 loop region by a highly conserved interaction loop (I loop) from Ski. The Ski binding surface on Smad4 significantly overlaps with tha...

MicroRNA (miR)-146a is known to be overexpressed in osteoarthritis (OA). However, the role of miR-146a in OA has not yet been fully elucidated. In the present study, we applied mechanical pressure of 10 MPa to human chondrocytes for 60 min in order to investigate the expression of miR-146a and apoptosis following the mechanical pressure injury. Normal human chondrocytes were transfected with an...

Transforming growth factor-beta/Smad pathway plays an important role in the pathogenesis of neurological diseases. This study investigated effects high fat diet and alcohol dependence on memory expression transforming prefrontal lobe, hippocampus cerebellum rats. Sixty male Sprague Dawley rats were randomly divided into control group, group alcohol+highfat group. Morris water maze test was perf...

Smad4 (DPC4) is a candidate tumor suppressor gene that has been hypothesized to be critical for transmitting signals from transforming growth factor (TGF) beta and related ligands. To directly test this hypothesis, the Smad4 gene was deleted through homologous recombination in human colorectal cancer cells. This deletion abrogated signaling from TGF-beta, as well as from the TGF-beta family mem...

Transforming growth factor beta (TGF-beta)/bone morphogenetic protein (BMP) signaling is crucial for regulating epithelial-mesenchymal interaction during organogenesis, and the canonical Smad pathway-mediated TGF-beta/BMP signaling plays important roles during development and disease. During tooth development, dental epithelial cells, known as Hertwig's epithelial root sheath (HERS), participat...

Unchecked cell growth is a hallmark of cancer. During oncogenesis, cancerous cells become resistant to the TGF-beta signaling pathway that usually keeps cell growth in check. The role of a critical mediator of this pathway, Smad4, in head and neck squamous cell carcinoma (HNSCC) remains unclear. In this issue of the JCI, Bornstein and colleagues report that Smad4 expression is decreased in mali...