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A Proximal Culture Method to Study Paracrine Signaling Between Cells
Published on: August 28, 2018
Transforming growth factor-β stimulates human ovarian cancer cell migration by up-regulating connexin43 expression
Xin Qiu1, Jung-Chien Cheng1, Jianfang Zhao1
1Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.
Abstract:
Reduced connexin43 (Cx43) expression is frequently detected in different types of human cancer. Cx43 has been shown to regulate cancer cell migration in a cell-type dependent manner. In both primary and recurrent human ovarian cancer, overexpression of TGF-β ligand and its receptors have been detected. TGF-β can regulate Cx43 expression in other cell types and stimulate human ovarian cancer cell migration. However, whether Cx43 can be regulated by TGF-β and is involved in TGF-β-stimulated cell migration in human ovarian cancer cells remain unknown. In this study, we demonstrate that TGF-β up-regulates Cx43 in two human ovarian cancer cell lines, SKOV3 and OVCAR4. The stimulatory effect of TGF-β on Cx43 expression is blocked by inhibition of TGF-β receptor. Treatment with TGF-β activates Smad2 and Smad3 signaling pathways in both ovarian cancer cell lines. In addition, siRNA-mediated knockdown of Smad2 or Smd3 abolishes TGF-β-induced up-regulation of Cx43 expression. Moreover, knockdown of Cx43 attenuates TGF-β-stimulated cell migration. This study demonstrates an important role for Cx43 in mediating the effects of TGF-β on human ovarian cancer cell migration.
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