Smad2 mediates Erk1/2 activation by TGF-beta1 in suspended, but not in adherent, gastric carcinoma cells.

Abstract

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-beta1 pathway. TGF-beta1 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-beta1-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-beta1-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-beta1, depending on cell adhesion status; TGF-beta1 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-beta1 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-beta1 was not different in suspension or in adhesion, and Smad7, but not the other Smads, activated PKB/Akt phosphorylation on TGF-beta1 treatment, indicating a specificity of Smad2-mediated and cell adhesion status-dependent activation of Erk1/2 activity.

• Authors: Mi-Sook Lee, Seong-Gyu Ko, Hwang-Phill Kim, Yong-Bae Kim, Sung-Yul Lee, Sang-Gyun Kim, Hyun-Soon Jong, Tae-You Kim, Jung Weon Lee, Yung-Jue Bang
• Journal: International journal of oncology (Int J Oncol) Vol. 24 Issue 5 Pg. 1229-34 (May 2004) ISSN: 1019-6439 [Print] Greece
• PMID: 15067346 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• RNA, Small Interfering
• Smad Proteins
• TGFB1 protein, human
• Trans-Activators
• Transforming Growth Factor beta
• Transforming Growth Factor beta1
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinases

Topics

• Cell Adhesion (drug effects, physiology)
• DNA-Binding Proteins (antagonists & inhibitors, metabolism)
• Enzyme Activation (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinases (metabolism)
• Phosphorylation
• RNA, Small Interfering (pharmacology)
• Signal Transduction
• Smad Proteins
• Stomach Neoplasms (metabolism, pathology)
• Trans-Activators (antagonists & inhibitors, metabolism)
• Transforming Growth Factor beta (pharmacology)
• Transforming Growth Factor beta1
• Tumor Cells, Cultured