<b>Dominant-negative p53 mutant R248Q increases the motile and invasive activities of oral squamous cell carcinoma</b><b> cells </b>

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Author(s)

    • NAKAZAWA Seitaro
    • Department of Gerodontology, Division of Oral Health Science, Graduate School of Dental Medicine
    • YAMAZAKI Yutaka
    • Department of Gerodontology, Division of Oral Health Science, Graduate School of Dental Medicine
    • SAKATA Ken-ichiro
    • Department of Oral Diagnosis and Oral Medicine, Division of Oral Pathobiological Science, Graduate School of Dental Medicine
    • LIANG Shanshan
    • The Key Laboratory of Biomarker High Throughput-Screening and Target Translation of Breast and Gastrointestinal Tumor, Oncology department of Affiliated Zhongshan Hospital of Dalian University
    • YOSHIKAWA Kazuhito
    • Department of Oral Diagnosis and Oral Medicine, Division of Oral Pathobiological Science, Graduate School of Dental Medicine
    • IIZASA Hisashi
    • Department of Microbiology, Shimane University Faculty of Medicine
    • HAMADA Jun-ichi
    • Health Sciences University of Hokkaido, School of Nursing and Social Services
    • KASHIWAZAKI Haruhiko
    • Section of Geriatric Dentistry and Perioperative Medicine in Dentistry, Division of Maxillofacial Diagnostic and Surgical Sciences Faculty of Dental Science
    • KITAGAWA Yoshimasa
    • Department of Oral Diagnosis and Oral Medicine, Division of Oral Pathobiological Science, Graduate School of Dental Medicine

Abstract

<p>The tumor suppressor gene <i>TP53</i> (gene) codes for a transcription factor which transactivates its target genes responsible for cell cycle arrest, DNA repair, apoptosis, and senescence. <i>TP53</i> is well known to be the most frequent target of genetic mutations in nearly half of human cancers including oral squamous cell carcinoma (OSCC). Many p53 mutants including R248Q and R248W not only lose its tumor-suppressor activities, but also interfere with the functions of wild-type p53; this is so-called dominant-negative (DN) mutation. The DN p53 mutation is a predictor of poor outcome in patients with various cancers, and also a risk factor for metastatic recurrence in patients with OSCC. Recently it has been reported that DN p53 mutants acquire new oncogenic activities, which is named gain-of-function (GOF). This study aimed at determining whether R248Q and R248W were involved in OSCC cells' acquiring aggressive phenotypes, using SAS, HSC4 and Ca9-22 cell lines. First, two mutants p53, R248Q and R248W, were respectively transfected into SAS cells harboring recessive-type p53 (E336X). As a result, SAS cells expressing R248Q showed highly spreading, motile and invasive activities compared to parent or mock-transfected cells whereas those expressing R248W did not increase those activities. Secondly, in HSC4 cells harboring R248Q and Ca9-22 cells harboring R248W, expressions of the mutants p53 were inhibited by the transfection with siRNAs targeting p53. The inhibition of the mutants p53 decreased spreading, motile and invasive activities of HSC4 cells whereas it did not affect those activities of Ca9-22 cells. These findings suggest that R248Q p53 mutation, but not R248W p53 mutation, induces more motile and invasive potentials in human OSCC cells.</p>

Journal

  • Biomedical Research

    Biomedical Research 40(1), 37-49, 2019

    Biomedical Research Press

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