RECQL1 and WRN Proteins Are Potential Therapeutic Targets in Head and Neck Squamous Cell Carcinoma

  • Akihito Arai
    Authors' Affiliations: 1Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Shiga; 2Department of Otolaryngology—Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto; and 3GeneCare Research Institute, Kanagawa, Japan
  • Tokuhiro Chano
    Authors' Affiliations: 1Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Shiga; 2Department of Otolaryngology—Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto; and 3GeneCare Research Institute, Kanagawa, Japan
  • Kazunobu Futami
    Authors' Affiliations: 1Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Shiga; 2Department of Otolaryngology—Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto; and 3GeneCare Research Institute, Kanagawa, Japan
  • Yasuhiro Furuichi
    Authors' Affiliations: 1Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Shiga; 2Department of Otolaryngology—Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto; and 3GeneCare Research Institute, Kanagawa, Japan
  • Kaichiro Ikebuchi
    Authors' Affiliations: 1Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Shiga; 2Department of Otolaryngology—Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto; and 3GeneCare Research Institute, Kanagawa, Japan
  • Takuma Inui
    Authors' Affiliations: 1Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Shiga; 2Department of Otolaryngology—Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto; and 3GeneCare Research Institute, Kanagawa, Japan
  • Hitosuke Tameno
    Authors' Affiliations: 1Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Shiga; 2Department of Otolaryngology—Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto; and 3GeneCare Research Institute, Kanagawa, Japan
  • Yasuko Ochi
    Authors' Affiliations: 1Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Shiga; 2Department of Otolaryngology—Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto; and 3GeneCare Research Institute, Kanagawa, Japan
  • Taketoshi Shimada
    Authors' Affiliations: 1Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Shiga; 2Department of Otolaryngology—Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto; and 3GeneCare Research Institute, Kanagawa, Japan
  • Yasuo Hisa
    Authors' Affiliations: 1Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Shiga; 2Department of Otolaryngology—Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto; and 3GeneCare Research Institute, Kanagawa, Japan
  • Hidetoshi Okabe
    Authors' Affiliations: 1Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Shiga; 2Department of Otolaryngology—Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto; and 3GeneCare Research Institute, Kanagawa, Japan

Description

<jats:title>Abstract</jats:title><jats:p>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. Cancer Res; 71(13); 4598–607. ©2011 AACR.</jats:p>

Journal

  • Cancer Research

    Cancer Research 71 (13), 4598-4607, 2011-06-30

    American Association for Cancer Research (AACR)

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