title: FOXM1 regulates proliferation, senescence and oxidative stress in keratinocytes and cancer cells.
abstract: Several transcription factors, including the master regulator of the epidermis, p63, are involved in controlling human keratinocyte proliferation and differentiation. Here, we report that in normal keratinocytes, the expression of FOXM1, a member of the Forkhead superfamily of transcription factors, is controlled by p63. We observe that, together with p63, FOXM1 strongly contributes to the maintenance of high proliferative potential in keratinocytes, whereas its expression decreases during differentiation, as well as during replicative-induced senescence. Depletion of FOXM1 is sufficient to induce keratinocyte senescence, paralleled by an increased ROS production and an inhibition of ROS-scavenger genes (SOD2, CAT, GPX2, PRDX). Interestingly, FOXM1 expression is strongly reduced in keratinocytes isolated from old human subjects compared with young subjects. FOXM1 depletion sensitizes both normal keratinocytes and squamous carcinoma cells to apoptosis and ROS-induced apoptosis. Together, these data identify FOXM1 as a key regulator of ROS in normal dividing epithelial cells and suggest that squamous carcinoma cells may also use FOXM1 to control oxidative stress to escape premature senescence and apoptosis.
authors.affiliation: University of Rome "Tor Vergata", Department of Experimental Medicine and Surgery, 00133, Rome, Italy.
authors.forename: Artem
authors.initials: A
authors.lastname: Smirnov
authors.affiliation: University of Rome "Tor Vergata", Department of Experimental Medicine and Surgery, 00133, Rome, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Panatta
authors.affiliation: University of Rome "Tor Vergata", Department of Experimental Medicine and Surgery, 00133, Rome, Italy.
authors.forename: AnnaMaria
authors.initials: A
authors.lastname: Lena
authors.affiliation: Istituto Dermopatico dell'Immacolata (IDI-IRCCS), 00166, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Castiglia
authors.affiliation: University of "Tor Vergata", Department of Systems Medicine, 00133, Rome, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Di Daniele
authors.affiliation: University of Rome "Tor Vergata", Department of Experimental Medicine and Surgery, 00133, Rome, Italy.
authors.forename: Gerry
authors.initials: G
authors.lastname: Melino
authors.affiliation: University of Rome "Tor Vergata", Department of Experimental Medicine and Surgery, 00133, Rome, Italy.|Istituto Dermopatico dell'Immacolata (IDI-IRCCS), 00166, Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Candi
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D016922:Cellular Senescence / Q000502:physiology*; D000072278:Forkhead Box Protein M1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015595:Skin Aging / Q000235:genetics / Q000473:pathology
chemical_list: C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D017382:Reactive Oxygen Species
keywords: FOXM1; head and neck cancer; oxidative stress; p63; senescence; skin