S-Space College of Medicine/School of Medicine (의과대학/대학원) Pathology (병리학전공) Journal Papers (저널논문_병리학전공)
Smad2 mediates Erk1/2 activation by TGF-ß1 in suspended, but not in adherent, gastric carcinoma cells
- Lee, Jung Weon; Lee, Mi-Sook; Ko, Seong-Gyu; Kim, Hwang-Phill; Kim, Yong-Bae; Lee, Sung-Yul; Kim, Sang-Gyun; Jong, Hyun-Soon; Kim, Tae-You; Bang, Yung-Jue
- Issue Date
- Spandidos Publications
- INTERNATIONAL JOURNAL OF ONCOLOGY 24: 1229-1234, 2004
- Integrin-mediated cell adhesion enables cells to respond to extracellular stimuli for diverse cellular functions including proliferation, leading to differential biological activities from cells in suspension. Integrins can transduce signals (directly) to intracellular molecules and also collaborate with other membrane receptor-mediated signal pathways, including TGF-ß1 pathway. TGF-ß1 induces growth inhibition in epithelial cells and is known to transduce intracellular signaling in Smad-dependent or -independent manner. Currently effects of cell adhesion status on the TGF-ß1-mediated Erk1/2 regulation and on its Smad-(in)dependency are not known. In this study, we examined effects of cell adhesion status on the TGF-ß1-mediated Erk1/2 regulation, and roles of Smad proteins on the cell adhesion-mediated effects, using a gastric carcinoma cell variant. First, we found that cell adhesion-dependent Erk1/2 activation responded differentially to TGF-ß1, depending on cell adhesion status; TGF-ß1 treatment resulted in activation of Erk1/2 in suspended cells, whereas a decrease was noted in adherent cells. This activation of Erk1/2 by TGF-ß1 in suspension was more enhanced by an overexpression of Smad2, but not of other Smads 2, 4, and 7, but abolished by a Smad2 reduction via an introduction of its siRNA. In contrast, PKB/Akt regulation by TGF-ß1 was not different in suspension or in adhesion, and Smad7, but not the other Smads, activated PKB/Akt phosphorylation on TGF-ß1 treatment, indicating a specificity of Smad2-mediated and cell adhesion statusdependent activation of Erk1/2 activity.