title: RECQL1 and WRN proteins are potential therapeutic targets in head and neck squamous cell carcinoma.
abstract: RECQL1 and WRN proteins are RecQ DNA helicases that participate in suppression of DNA hyper-recombination and repair. In this study, we report evidence supporting their candidacy as cancer therapeutic targets. In hypopharyngeal carcinomas, which have the worst prognosis among head and neck squamous cell carcinomas (HNSCC) that are rapidly rising in incidence, we found that RECQL1 and WRN proteins are highly expressed and that siRNA-mediated silencing of either gene suppressed carcinoma cell growth in vitro. Similarly, siRNA administration in a murine xenograft model of hypopharyngeal carcinoma markedly inhibited tumor growth. Moreover, combining either siRNA with cis-platinum (II) diammine dichloride significantly augmented the in vivo anticancer effects of this drug that is used commonly in HNSCC treatment. Notably, we observed no recurrence of some tumors following siRNA treatment in this model. Our findings offer a preclinical proof of concept for RECQL1 and WRN proteins as novel therapeutic targets to treat aggressive HNSCC and perhaps other cancers.
authors.affiliation: Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Arai
authors.forename: Tokuhiro
authors.initials: T
authors.lastname: Chano
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Futami
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Furuichi
authors.forename: Kaichiro
authors.initials: K
authors.lastname: Ikebuchi
authors.forename: Takuma
authors.initials: T
authors.lastname: Inui
authors.forename: Hitosuke
authors.initials: H
authors.lastname: Tameno
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Ochi
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Shimada
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hisa
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Okabe
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000628:therapy*; D002294:Carcinoma, Squamous Cell; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D003131:Combined Modality Therapy; D005090:Exodeoxyribonucleases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D020868:Gene Silencing; D006367:HeLa Cells; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000628:therapy*; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D058990:Molecular Targeted Therapy / Q000379:methods*; D018307:Neoplasms, Squamous Cell / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000628:therapy*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D011897:Random Allocation; D053484:RecQ Helicases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck; D000071657:Werner Syndrome Helicase; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase; D002945:Cisplatin