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Cancer Research 67, 7551-7555, August 15, 2007. doi: 10.1158/0008-5472.CAN-07-0881
© 2007 American Association for Cancer Research

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4E-Binding Protein 1: A Key Molecular "Funnel Factor" in Human Cancer with Clinical Implications

Gemma Armengol1, Federico Rojo1, Josep Castellví1, Carmela Iglesias1, Miriam Cuatrecasas1, Berta Pons1, José Baselga2 and Santiago Ramón y Cajal1

Departments of 1 Pathology and 2 Oncology, Vall d'Hebron University Hospital, Barcelona, Spain

Requests for reprints: Santiago Ramón y Cajal, Department of Pathology, Vall d'Hebron University Hospital, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain. Phone: 34-932746824; Fax: 34-934894015; E-mail: sramon{at}vhebron.net.

In an attempt to identify molecules that clearly reflect the oncogenic role of cell signaling pathways in human tumors, we propose a concept we term "funnel factor", a factor where several oncogenic signals converge and drive the proliferative signal downstream. In studies done in various tumor types, the expression of key cell signaling factors, including Her1 and Her2 growth factor receptors, as well as the RAS-RAF-mitogen-activated protein kinase and the phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathways was correlated with the associated clinicopathologic characteristics of these tumors. The downstream factors p70, S6, 4E-binding protein 1 (4E-BP1), and eukaryotic translation initiation factor 4E, which play a critical role in the control of protein synthesis, survival, and cell growth, were also analyzed. We found that phosphorylated 4E-BP1 (p-4E-BP1) expression in breast, ovary, and prostate tumors is associated with malignant progression and an adverse prognosis regardless of the upstream oncogenic alterations. Thus, p-4E-BP1 seems to act as a funnel factor for an essential oncogenic capability of tumor cells, self-sufficiency in growth signals, and could be a highly relevant molecular marker of malignant potential. Further investigation into this concept may identify additional funnel factors in the oncogenic pathways and provide potential therapeutic targets. [Cancer Res 2007;67(16):7551–5]




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Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2007 by the American Association for Cancer Research.