Human recombinant Cripto-1 increases doubling time and reduces proliferation of HeLa cells independent of pro-proliferation pathways

Human oncofetal protein Cripto-1 (CR-1) is overexpressed in many types of cancers. CR-1 binds to cell surface Glypican-1 to activate Erk1/2 MARK and Akt pathways leading to cell proliferation. However, we show that treatment with recombinant CR-1 reduces proliferation of HeLa cells by increasing the doubling time without triggering cell death or cell cycle arrest. Using a comparative study with U-87 MG cells, we show that the pro-proliferative pathway of CR-1 is not effective in HeLa cells due to lower expression of Glypican-1. Further we show that treatment with recombinant CR-1 increases PTEN in HeLa cells leading to downregulation of PI3K/Akt pathway. The anti-proliferative effect gets potentiated when the pro-proliferative pathway is blocked. (C) 2011 Elsevier Ireland Ltd. All rights reserved.