Cripto-1 induces phosphatidylinositol 3'-kinase-dependent phosphorylation of AKT and glycogen synthase kinase 3β in human cervical carcinoma cells

Andreas D. Ebert, Christian Wechselberger, Stephan Frank, Brenda Wallace-Jones, Masaharu Seno, Isabel Martinez-Lacaci, Caterina Bianco, Marta De Santis, Hans K. Weitzel, David S. Salomon

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Abstract

Cripto-1 (CR-1), a member of the epidermal growth factor-CFC peptide family, activates the ras/raf/mitogen-activated protein/extracellular signal- regulated kinase/mitogen-activated protein kinase pathway. In the present study, the role of CR-1 in the phosphatidylinositol 3'-kinase (PI3K)/AKT (protein kinase B)/glycogen synthase kinase 3β (GSK-3β)dependent signaling pathway was evaluated in human SiHa cervical carcinoma cells. Our data demonstrate that CR-1 can enhance the tyrosine phosphorylation of the p85 regulatory subunit of PI3K and transiently induce the phosphorylation of AKT in a time- and dose-dependent manner. In addition, CR-1 was found to induce the phosphorylation of GSK-3β. Phosphorylation of AKT and GSK-3β by CR-1 can be blocked by LY294002, a specific inhibitor of PI3K, thus leading to apoptosis. Finally, the apoptotic effect of LY294002 can be partially rescued by exogenous CR-1. In summary, our data suggest that human CR-1 may function as a survival factor through a PI3K-dependent signaling pathway involving AKT and GSK-3β.

Original languageEnglish
Pages (from-to)4502-4505
Number of pages4
JournalCancer Research
Volume59
Issue number18
Publication statusPublished - Sep 15 1999

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ebert, A. D., Wechselberger, C., Frank, S., Wallace-Jones, B., Seno, M., Martinez-Lacaci, I., Bianco, C., De Santis, M., Weitzel, H. K., & Salomon, D. S. (1999). Cripto-1 induces phosphatidylinositol 3'-kinase-dependent phosphorylation of AKT and glycogen synthase kinase 3β in human cervical carcinoma cells. Cancer Research, 59(18), 4502-4505.