RNAi screens identify CHD4 as an essential gene in breast cancer growth

摘要: // Carolina D’Alesio 1, * , Simona Punzi Angelo Cicalese 1 Lorenzo Fornasari Laura Furia Riva 2 Alessandro Carugo 3 Giuseppe Curigliano 4 Carmen Criscitiello Giancarlo Pruneri 5, 6 Pier Pelicci 7 Mario Faretta Daniela Bossi Luisa Lanfrancone Department of Experimental Oncology, European Institute Milan 20141, Italy Center for Genomic Science IIT@SEMM, Fondazione Istituto Italiano di Tecnologia, 20139, Molecular and Cellular UT MD Anderson Cancer Center, Houston, TX 77030, USA Division Therapeutics, 5 School Medicine, University Milan, 20122, Biobank Translational Medicine Unit, Pathology, These authors have contributed equally to this work Correspondence to: Lanfrancone, email: luisa.lanfrancone@ieo.eu Keywords: RNAi screen, epigenetic targets, breast cancer, CHD4, in vivo murine human models Received: July 22, 2016     Accepted: September 29, Published: October 13, 2016 ABSTRACT Epigenetic regulation plays an essential role tumor development modifiers are considered optimal potential druggable candidates. In order identify new cancer vulnerabilities improve therapeutic chances patients, we performed vitro shRNA screens a cell model (MCF10DCIS.com line) using libraries. Among the genes identified our screening, deeply investigated Chromodomain Helicase DNA binding Protein ( CHD4 ) tumorigenesis. silencing significantly reduced growth proliferation MCF10DCIS.com cells. Similarly, was decreased spontaneous mouse carcinoma (MMTV-NeuT system) metastatic patient-derived xenograft models. Conversely, no reduction proliferative ability non-transformed mammary epithelial cells (MCF10A) detected. Moreover, showed that depletion arrests by inducing G0/G1 block cycle associated with up-regulation CDKN1A (p21). results highlight relevance genetic identification frailties as pharmacological target inhibit growth.