Synergistic interaction between AKT and Notch-1 signaling in cervical cancer: a critical role in tumor cell migration and invasion

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AJBM  Volume 2, Issue 2, pages 200–211, February 2014               Full Text-PDF 

Willem B. Doshi, Peter G. Thury,  Rui Chen, Jone A. Fishbein,  Micheal K. Foley


Aberrant Notch signaling has been repeatedly demonstrated to facilitate the proliferation and survival of tumorigenesis by regulating downstream effectors or other signaling pathways. We hypothesized that Notch-1 could promote cervical cancer cell migration and invasion by stimulating β-catenin and NF-κB signaling via AKT activation. Notch-1 was highly expressed in cervical cancer specimens from 76 women, compared with normal cervical tissues, and this expression was correlated with elevated AKT phosphorylation. Furthermore, the activation of Notch-1 by DLL4 stimulation resulted in AKT activation and thereby promoted β-catenin activity and NF-κB signaling. These results indicate that Notch activation could stimulate β-catenin and NF-κB signaling through AKT activation in cervical cancer cells. Increased nuclear translocation of β-catenin can result in accelerated tumor cell invasion. It has also been shown that AKT can induce IKK activation through an interaction with IKK that leads to the translocation of NF-κB to the nucleus. We conclude that the synergistic interaction between AKT and Notch1 signaling in cervical cancer cells plays a critical role in cervical cancer cell migration and invasion.

Key words: Cervical cancer, Notch signaling, AKT, NF-κB, IKK activation