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

Biomedical Research
Seitaro NakazawaYutaka Yamazaki

Abstract

The tumor suppressor gene TP53 (gene) codes for a transcription factor which transactivates its target genes responsible for cell cycle arrest, DNA repair, apoptosis, and senescence. TP53 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 e...Continue Reading

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Citations

Jul 17, 2019·Journal of Experimental & Clinical Cancer Research : CR·Matilde Clarissa MalfattiGianluca Tell
Aug 25, 2020·Cancer Cell International·Xiao-Han LiYa-Ping Fu
Mar 1, 2021·Biochemical and Biophysical Research Communications·Tetsuo KiguchiMakio Saeki
Mar 25, 2021·Cell Biology International·Surendar AravindhanMajid Ahmadi

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