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Abstract
Giulio Bizzozero classified the tissues concerning their capacity to self-renew during the adult life in labile, stable and permanent tissues. In 1940 Viktor Hamburger and Rita Levi Montalcini exposed the possibility to induce the growth of permanent cells thanks to a specific ligand Nerve Growth Factor (NGF). Stanley Cohen purified a protein the Epidermal Growth Factor (EGF), able to induce epidermis proliferation and to elicit precocious eye disclosure and teeth eruption, establishing the “inverse” relationships between the proliferation and differentiation. These two biological effects induced by EGF were according to EGFR signaling is involved in a large array of cellular functions such as proliferation, survival, adhesion, migration and differentiation. This review is focused on the key role of growth factors signaling and their downstream effectors in physiological and in pathological phenomena, the authors highlight the governance of Growth factors during the EMT in cancer invasion.
Highlights
Stanley Cohen purified a protein the Epidermal Growth Factor (EGF), able to induce epidermis proliferation and to elicit precocious eye disclosure and teeth eruption, establishing the “inverse” relationships between the proliferation and differentiation. These two biological effects induced by EGF were according to EGFR signaling is involved in a large array of cellular functions such as proliferation, survival, adhesion, migration and differentiation
This review is focused on the key role of growth factors signaling and their downstream effectors in physiological and in pathological phenomena, the authors highlight the governance of Growth factors during the Epithelial Mesenchymal Transition (EMT) in cancer invasion
Cadherins genes activated in embryogenesis are activated during carcinoma progression and metastasis, indicating that EMT involves a reactivation during tumor progression
Summary
Stanley Cohen described on “The Journal of Biological Chemistry” a protein called Epidermal Growth Factor (EGF) able to induce epidermis proliferation and to elicit precocious eye disclosure and teeth eruption [1].Some years later it was discovered that radioactivity of labelled EGF may be localized in many tissues (e.g. epidermis, corneal epithelium, liver, mammary gland) so it was described an EGF pleyotropic action [2,3,4,5]; just 30 years ago on 1986 the Nobel Committee proclaimed Stanley Cohen and Rita Levi-Montalcini, the first scientist who discovered the Nerve Growth Factor, winners of the prize for Medicine and Physiology.The interaction between epithelial and stromal cells is crucial for differentiation and epithelial growth in the course of morphogenesis, embryonal stage and in wound healing of various tissues [6, 7]. Insulin-like growth factor 2 (IGF2y) can induce, both morphogenesis in different organisms as well as, the development and growth of many tumor entities. Most oncogenic pathways mediated by peptide mitogens FGF, EGF, TGF-α and IGF2y, and Src, Ras, Ets, Integrin, Wnt/ b-catenin and Notch signalings, can promote Epithelial Mesenchymal Transition (EMT) [8] (Figure 1A-1B). Growth factors activity overlaps with the Cadherinsreported to be involved in EMT.The elucidation of the various processes that modulate Cadherins and Growth Factor Receptors (GFR) signal transduction, like receptor heterodimerization and endocytosis, has highlightened new therapeutic opportunities and focused the mechanisms contributing to the effectiveness of existing anticancer treatments [9]. The involvement of cadherins is recognized in the normal epithelial tissue organization and in cancer promoting as discussed previously [10]. The authors purpose is to emphasize the governance of growth factor receptors in progression and cancer invasion
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