SMAD5 is a receptor-regulated SMAD (R-SMAD) protein that primarily transduces signals from the bone morphogenetic protein (BMP) family of cytokines.
SMAD5, together with SMAD1 and SMAD8, is activated by BMP receptors. Once phosphorylated, it forms complexes with the common mediator SMAD4.
In some studies, altered or reduced SMAD5 expression has been linked with the loss of BMP-mediated tumor-suppressive functions. This could, for example, compromise normal differentiation signals and enable unchecked proliferation.
Conversely, in contexts where active BMP signaling may promote aspects of tumor progression (such as invasion or metastasis), altered activity or overexpression of SMAD5 may correlate with aggressive cancer phenotypes.
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