title: The Interplay of Reactive Oxygen Species, Hypoxia, Inflammation, and Sirtuins in Cancer Initiation and Progression.
abstract: The presence of ROS is a constant feature in living cells metabolizing O2. ROS concentration and compartmentation determine their physiological or pathological effects. ROS overproduction is a feature of cancer cells and plays several roles during the natural history of malignant tumor. ROS continuously contribute to each step of cancerogenesis, from the initiation to the malignant progression, acting directly or indirectly. In this review, we will (a) underline the role of ROS in the pathway leading a normal cell to tumor transformation and progression, (b) define the multiple roles of ROS during the natural history of a tumor, (c) conciliate many conflicting data about harmful or beneficial effects of ROS, (d) rethink the importance of oncogene and tumor suppressor gene mutations in relation to the malignant progression, and (e) collocate all the cancer hallmarks in a mechanistic sequence which could represent a "physiological" response to the initial growth of a transformed stem/pluripotent cell, defining also the role of ROS in each hallmark. We will provide a simplified sketch about the relationships between ROS and cancer. The attention will be focused on the contribution of ROS to the signaling of HIF, NFκB, and Sirtuins as a leitmotif of cancer initiation and progression.
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy; Department of Cellular and Molecular Pathology, IRCCS San Raffaele, 00166 Rome, Italy.
authors.forename: Marco
authors.identifier: 0000-0001-7128-810X
authors.initials: M
authors.lastname: Tafani
authors.affiliation: Department of Cellular and Molecular Pathology, IRCCS San Raffaele, 00166 Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Sansone
authors.affiliation: Consortium MEBIC, San Raffaele University, 00166 Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Limana
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Tania
authors.initials: T
authors.lastname: Arcangeli
authors.affiliation: Department of Gynecological-Obstetrical Sciences and Urological Sciences, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: De Santis
authors.affiliation: Department of Human Anatomy, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Polese
authors.affiliation: Department of Cellular and Molecular Pathology, IRCCS San Raffaele, 00166 Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Fini
authors.affiliation: Consortium MEBIC, San Raffaele University, 00166 Rome, Italy.
authors.forename: Matteo A
authors.initials: MA
authors.lastname: Russo
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000378:metabolism*; D007249:Inflammation / Q000150:complications / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D037761:Sirtuins / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D037761:Sirtuins