|
Fig. 4
JAM-A activated TGF-β/NODAL signaling. (A,B) In JAM-A-transfected DB cells (A) and DLBCL patients (B), JAM-A overexpression was related to activation of TGF-β/NODAL signaling. (C) As assessed by Whole-mount in Situ Hybridization and real-time quantitative RT-PCR, ndr-1 and ndr-2 were increased in jam-1-overexpressing zebrafish. WT, wild type. (D) JAM-A upregulated NODAL expression, which was restored by specific TGF-β/NODAL/Smad inhibitor SB431542 or JAM-A ShRNA. SB431542 abrogated JAM-A-induced lymphoma cell invasion (E) JAM-A was the highest in patients with involvement of endoderm-derived organs, followed by those with involvement of mesoderm- and ectoderm-derived organs. (F) JAM-A correlated with increased NODAL expression in primary lymph nodes, as well as in secondary lesions. Data in (C) are representative of three independent experiments.