RECQL1 and WRN proteins are potential therapeutic targets in head and neck squamous cell carcinoma

Cancer Res. 2011 Jul 1;71(13):4598-607. doi: 10.1158/0008-5472.CAN-11-0320. Epub 2011 May 13.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma / drug therapy
  • Carcinoma / enzymology*
  • Carcinoma / genetics
  • Carcinoma / therapy*
  • Carcinoma, Squamous Cell
  • Cell Death / drug effects
  • Cell Death / genetics
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Combined Modality Therapy
  • Exodeoxyribonucleases / antagonists & inhibitors*
  • Exodeoxyribonucleases / biosynthesis
  • Exodeoxyribonucleases / genetics
  • Gene Silencing
  • HeLa Cells
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / enzymology*
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Hypopharyngeal Neoplasms / drug therapy
  • Hypopharyngeal Neoplasms / enzymology*
  • Hypopharyngeal Neoplasms / genetics
  • Hypopharyngeal Neoplasms / therapy*
  • Mice
  • Mice, Inbred BALB C
  • Molecular Targeted Therapy / methods*
  • Neoplasms, Squamous Cell / drug therapy
  • Neoplasms, Squamous Cell / enzymology*
  • Neoplasms, Squamous Cell / genetics
  • Neoplasms, Squamous Cell / therapy*
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • Random Allocation
  • RecQ Helicases / antagonists & inhibitors*
  • RecQ Helicases / biosynthesis
  • RecQ Helicases / genetics
  • Squamous Cell Carcinoma of Head and Neck
  • Werner Syndrome Helicase
  • Xenograft Model Antitumor Assays


  • RNA, Small Interfering
  • Exodeoxyribonucleases
  • RecQ Helicases
  • WRN protein, human
  • Werner Syndrome Helicase
  • Cisplatin