Cancers, Vol. 11, Pages 1582: CAF-1 Subunits Levels Suggest Combined Treatments with PARP-Inhibitors and Ionizing Radiation in Advanced HNSCC

Cancers, Vol. 11, Pages 1582: CAF-1 Subunits Levels Suggest Combined Treatments with PARP-Inhibitors and Ionizing Radiation in Advanced HNSCC Cancers doi: 10.3390/cancers11101582 Authors: Francesco Morra Francesco Merolla Ida Picardi Daniela Russo Gennaro Ilardi Silvia Varricchio Federica Liotti Roberto Pacelli Luca Palazzo Massimo Mascolo Angela Celetti Stefania Staibano Oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinomas show high morbidity and mortality rates. We aimed to investigate the role of the “Chromatin Assembly Factor-1” (CAF-1) p60 and p150 subunits, involved in DNA repair and replication, in OSCC and OPSCC progression and in response to Poly(ADP-ribose) polymerase (PARP)-inhibitors and exposure to ionizing radiation (IR). We immunostained tissue microarrays (TMAs), including 112 OSCC and 42 OPSCC, with anti-CAF-1/p60 and anti-CAF-1/p150 specific antibodies, correlating their expression with prognosis. Moreover, we assessed the sensitivity to PARP inhibitors and the double-strand breaks repair proficiency by cell viability and HR reporter assays, respectively, in HPV-positive and HPV-negative cell lines upon CAF-1/p60 and CAF-1/p150 depletion. The immunohistochemical analysis revealed a significant prognostic value of both tissue biomarkers combined expression in OSCC but not in OPSCC. In in vitro studies, the p60/150 CAF-1 subunits’ depletion impaired the proficiency of Homologous ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research