title: 4E-binding protein 1: a key molecular "funnel factor" in human cancer with clinical implications.
abstract: 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.
authors: Department of Pathology, Vall d'Hebron University Hospital, Barcelona, Spain.
authors: Gemma
authors: G
authors: Armengol
authors: Federico
authors: F
authors: Rojo
authors: Josep
authors: J
authors: Castellví
authors: Carmela
authors: C
authors: Iglesias
authors: Miriam
authors: M
authors: Cuatrecasas
authors: Berta
authors: B
authors: Pons
authors: José
authors: J
authors: Baselga
authors: Santiago
authors: S
authors: Ramón y Cajal
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D018797:Cell Cycle Proteins; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D010750:Phosphoproteins / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins