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

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• 作者：Asim Bikas Das ; Pojul Loying ; Biplab Bose ; ^{biplabbose@iitg.ernet.in}
• 关键词：Cripto-1 ; Glypican-1 ; Cell proliferation ; JNK ; PTEN ; HeLa
• 刊名：Cancer Letters
• 出版年：2012
• 期刊代码：44_03043835
• 类别：med
• 出版时间：28 May, 2012
• 卷：318
• 期：2
• 页码：189-198
• 文件大小：1084 K

摘要

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 MAPK 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.