Molecular Cancer Research 3:227-236 (2005)
© 2005 American Association for Cancer Research
Signaling and Regulation
Akt Activation, but not Extracellular Signal–Regulated Kinase Activation, Is Required for SDF-1
/CXCR4–Mediated Migration of Epitheloid Carcinoma Cells
Sheng-Bin Peng,
Victoria Peek,
Yan Zhai,
Donald C. Paul,
Qinyuan Lou,
Xiaoling Xia,
Thomas Eessalu,
Wayne Kohn and
Shaoqing Tang
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana
Requests for reprints: Sheng-Bin Peng, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285. Phone: 317-433-4549; Fax: 317-276-1414. E-mail: Peng_Sheng-Bin{at}Lilly.com
Emerging evidence shows that the stromal cell–derived factor 1 (SDF-1)/CXCR4 interaction regulates multiple cell signaling pathways and a variety of cellular functions such as cell migration, proliferation, and survival. There is little information linking the cellular functions and individual signaling pathways mediated by SDF-1 and CXCR4 in human cancer cells. In this study, we have shown that human epitheloid carcinoma HeLa cells express functional CXCR4 by reverse transcription-PCR, immunofluorescent staining, and 125I-SDF-1
ligand binding analyses. The treatment of HeLa cells with recombinant SDF-1 results in time-dependent Akt and extracellular signal–regulated kinase 1/2 (ERK1/2) activations. The SDF-1–induced Akt and ERK1/2 activations are CXCR4 dependent as confirmed by their total inhibition by T134, a CXCR4-specific peptide antagonist. Cell signaling analysis with pathway-specific inhibitors reveals that SDF-1–induced Akt activation is not required for ERK1/2 activation and vice versa, indicating that activations of Akt and ERK1/2 occur independently. Functional analysis shows that SDF-1 induces a CXCR4-dependent migration of HeLa cells. The migration can be totally blocked by phosphoinositide 3-kinase inhibitors, wortmannin or LY294002, whereas mitogen-activated protein/ERK kinase inhibitors, PD98059 and U0126, have no significant effect on SDF-1–induced migration, suggesting that Akt activation, but not ERK1/2 activation, is required for SDF-1–induced migration of epitheloid carcinoma cells.
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Copyright © 2005 by the American Association for Cancer Research.
