TI - 4E -binding protein 1 : a key molecular "funnel factor" in human cancer with clinical implications . AB - 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 .