Y-Box Binding Protein-1 Enhances Oncogenic Transforming Growth Factor Beta Signaling In Breast Cancer Cells Via Triggering Phospho-Activation Of Smad2

Background/Aim: Transforming growth factor beta (TGF beta) plays a role in diverse oncogenic pathways including cell proliferation and cell motility and is regulated by the pleiotropic factor Y-box binding protein-1 (YB-1). In breast cancer, Sma/Mad related protein 2 (Smad2) represents the most common downstream transducer in TGF beta signaling. Materials and Methods: Here, YB-1's impact on Smad2 phosphoactivation was characterized by incubation of the breast cancer cell line MCF-7 with or without TGF beta 1 in the absence or presence of overexpressed YB-1 protein. The phospho-status of Smad2 was assessed via western blotting. Results: Analysis of MCF-7 cells revealed no induction of total Smad2 neither in the presence of TGF beta 1, nor during YB-1 overexpression. In contrast, incubation with TGF beta 1 led to an increase of phosphorylated Smad2 forms which was significantly amplified by simultaneously overexpressed YB-1 (2.8 +/- 0.2-fold). Conclusion: Oncogenic YB-1 indirectly enhances TGF beta signaling cascades via Smad2 phospho-activation and may represent a promising factor for future diagnosis and therapy of breast cancer.