A Loss of Smad2 dependent TGF-beta signaling correlates with poor differentiation in gastric cancer

Background: TGF-beta plays dual roles in progression of human cancer. In precancerous stages, TGF-beta acts as tumor suppressor by providing cytostatic downstream signaling, whereas in late cancer stages, it induces processes that support tumor progression, including stroma fibroblast activation, epithelial mesenchymal transition and metastasis. Due to the high complexity of the TGF-beta signaling pathway, molecular details of this dramatic functional switch are only poorly understood. Recently, a shift from Smad2/3 C-terminal to linker site phosphorylation was hypothesized as key event for the cancer facilitati…