title: XPC silencing in normal human keratinocytes triggers metabolic alterations through NOX-1 activation-mediated reactive oxygen species.
abstract: Cancer cells utilize complex mechanisms to remodel their bioenergetic properties. We exploited the intrinsic genomic stability of xeroderma pigmentosum C (XPC) to understand the inter-relationships between genomic instability, reactive oxygen species (ROS) generation, and metabolic alterations during neoplastic transformation. We showed that knockdown of XPC (XPC(KD)) in normal human keratinocytes results in metabolism remodeling through NADPH oxidase-1 (NOX-1) activation, which in turn leads to increased ROS levels. While enforcing antioxidant defenses by overexpressing catalase, CuZnSOD, or MnSOD could not block the metabolism remodeling, impaired NOX-1 activation abrogates both alteration in ROS levels and modifications of energy metabolism. As NOX-1 activation is observed in human squamous cell carcinomas (SCCs), the blockade of NOX-1 could be a target for the prevention and the treatment of skin cancers.
authors.affiliation: Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. hamidreza.rezvani@u-bordeaux2.fr
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Rezvani
authors.forename: Rodrigue
authors.initials: R
authors.lastname: Rossignol
authors.forename: Nsrein
authors.initials: N
authors.lastname: Ali
authors.forename: Giovanni
authors.initials: G
authors.lastname: Benard
authors.forename: Xiuwei
authors.initials: X
authors.lastname: Tang
authors.forename: Hee Seung
authors.initials: HS
authors.lastname: Yang
authors.forename: Thomas
authors.initials: T
authors.lastname: Jouary
authors.forename: Hubert
authors.initials: H
authors.lastname: de Verneuil
authors.forename: Alain
authors.initials: A
authors.lastname: Taïeb
authors.forename: Arianna L
authors.initials: AL
authors.lastname: Kim
authors.forename: Frédéric
authors.initials: F
authors.lastname: Mazurier
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000235:genetics; D008954:Models, Biological; D008969:Molecular Sequence Data; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000378:metabolism* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D034622:RNA Interference / Q000187:drug effects / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000009:adverse effects* / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid
chemical_list: D000975:Antioxidants; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C086984:XPC protein, human; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C402799:NOX1 protein, human