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00085472can110320-sup-sfig_2.pdf (4.67 MB)

Supplementary Figure 2 from RECQL1 and WRN Proteins Are Potential Therapeutic Targets in Head and Neck Squamous Cell Carcinoma

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posted on 2023-03-30, 20:22 authored by Akihito Arai, Tokuhiro Chano, Kazunobu Futami, Yasuhiro Furuichi, Kaichiro Ikebuchi, Takuma Inui, Hitosuke Tameno, Yasuko Ochi, Taketoshi Shimada, Yasuo Hisa, Hidetoshi Okabe
Supplementary Figure 2 from RECQL1 and WRN Proteins Are Potential Therapeutic Targets in Head and Neck Squamous Cell Carcinoma

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ARTICLE 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. Cancer Res; 71(13); 4598–607. ©2011 AACR.

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    Cancer Research

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    Biological Agents & TherapiesGene therapyDrug MechanismsDrug-mediated stimulation of cell death pathwaysDrug TargetsOncoprotein & tumor suppressor drug targetsGenome BiologySilencing and reactivation of gene expressionHead, Neck & Oral CancersPreclinical ModelsXenograft modelsRadiobiologyRadiation-induced DNA damage

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