p63 and ZNF148 cooperate to regulate head and neck squamous cell carcinoma
Abstract
Head and neck squamous cell carcinoma (HNSCC) is a common and aggressive malignancy. While significant advances have been made in the management of low-grade cancer, treatment of advanced HNSCC remains challenging. Here, we used a proteomic approach to find binding partners of the oncogene p63, the most frequently amplified transcription factor in HNSCC. We identified a zinc finger protein, ZNF148, which is coexpressed and physically binds p63 in carcinoma cells. Genome occupancy analyses identified a functional transcribed enhancer-derived RNA (eRNA) upstream of the CCND1 gene occupied by both factors. Mechanistically, p63 and ZNF148 control transcription of this eRNA, leading to overexpression of cyclin D1 to reinforce tumor cell proliferation. Importantly, this axis is specific for cancer cells and remains inactive in normal epithelial cells. The expression levels of these factors and the eRNA are positively correlated in cancer and associated with advanced stage and metastasis. Collectively, our data reveal a molecular pathway controlling HNSCC progression and identify potential selective targets for cancer treatment.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (22)
Rosalba Pecorari
Department of Experimental Medicine, Tor Vergata Oncoscience Research, University of Rome Tor Vergata
Mara Mancini
Department of Experimental Medicine, University of Rome “Tor Vergata”
Artem Smirnov
Department of Experimental Medicine, University of Rome “Tor Vergata”
Giacomo Corleone
Struttura di Area Funzionale di Ricerca Unit (SAFU), Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Istituto di Ricovero e Cura a Carattere Scientifico Regina Elena National Cancer Institute
Flavia Novelli
Department of Experimental Medicine, University of Rome “Tor Vergata”
Anna Maria Lena
Department of Experimental Medicine, University of Rome “Tor Vergata”
Mariacristina Franzese Canonico
Department of Experimental Medicine, University of Rome “Tor Vergata”
Manuela Montanaro
Department of Experimental Medicine, University of Rome “Tor Vergata”
Angela Cappello
Department of Experimental Medicine, University of Rome “Tor Vergata”
Andrea Sacconi
Biostatistics, Bioinformatics and Clinical Trial Center, Istituto di Ricovero e Cura a Carattere Scientifico Regina Elena National Cancer Institute
Gabriella Misso
Department of Precision Medicine, University of Campania Luigi Vanvitelli
Michela Falco
Department of Precision Medicine, University of Campania Luigi Vanvitelli
Chiara Tammaro
Fabiola Ciccosanti
National Institute for Infectious Diseases, Istituto di Ricovero e Cura a Carattere Scientifico “Lazzaro Spallanzani”
Mauro Piacentini
National Institute for Infectious Diseases, Istituto di Ricovero e Cura a Carattere Scientifico “Lazzaro Spallanzani”
Manuel Scimeca
Department of Experimental Medicine, University of Rome “Tor Vergata”
Michele Caraglia
Department of Precision Medicine, University of Campania Luigi Vanvitelli
Giovanni Blandino
Translational Oncology Research Unit, Department of Research, Diagnosis and Innovative Technologies, Istituto di Ricovero e Cura a Carattere Scientifico Regina Elena National Cancer Institute
Alessandro Mauriello
Department of Experimental Medicine, University of Rome “Tor Vergata”
Maurizio Fanciulli
Struttura di Area Funzionale di Ricerca Unit (SAFU), Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Istituto di Ricovero e Cura a Carattere Scientifico Regina Elena National Cancer Institute
Gerry Melino
Department of Experimental Medicine, TOR, University of Rome “Tor Vergata”
Eleonora Candi
Department of Experimental Medicine, University of Rome “Tor Vergata”