S100A4 interacts with mutant p53 and affects gastric cancer MKN1 cell autophagy and differentiation.
The acquired p53 mutations are the most common genetic alterations in human cancers. Mutant p53 proteins tend to accumulate, augmenting their oncogenic potential. However, the mechanisms for mutant p53 accumulation are not known. Previous studies have shown that S100A4 interacts with wild‑type p53. The present study marks the first time the effect of S100A4 on mutant p53 levels in gastric cancer MKN1 cells, which harbor mutant p53V143A, and the functional consequences have been investigated. S100A4 interacted with mutant p53V143A in the cells, and S100A4 inhibition decreased mutant p53V143A levels, indicating that S100A4 promoted mutant p53 accumulation through their interaction. We also found that S100A4 inhibition altered the expression of the mutant p53V143A target genes [c-Myc and inhibitor of DNA binding 2 (Id2)]. Moreover, we demonstrated that S100A4 knockdown increased mutant p53-related autophagy and cell differentiation. In conclusion, our data suggest a novel mechanism for mutant p53V143A accumulation and add a new facet to the role of S100A4 in cancer.
Department of Medical Genetics, China Medical University, Shenyang North New Area, Shenyang, Liaoning 110122, P.R. China.
Wei
W
Shen
Department of Medical Genetics, China Medical University, Shenyang North New Area, Shenyang, Liaoning 110122, P.R. China.
Danqi
D
Chen
Department of Medical Genetics, China Medical University, Shenyang North New Area, Shenyang, Liaoning 110122, P.R. China.
Shanshan
S
Liu
Department of Medical Genetics, China Medical University, Shenyang North New Area, Shenyang, Liaoning 110122, P.R. China.
Lisha
L
Chen
Department of Medical Genetics, China Medical University, Shenyang North New Area, Shenyang, Liaoning 110122, P.R. China.
Aiwen
A
Yu
Department of Medical Genetics, China Medical University, Shenyang North New Area, Shenyang, Liaoning 110122, P.R. China.
Hao
H
Fu
Department of Medical Genetics, China Medical University, Shenyang North New Area, Shenyang, Liaoning 110122, P.R. China.
Xiuju
X
Sun
D001343:Autophagy / Q000235:genetics*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006801:Humans; D047468:Immunoprecipitation; D009154:Mutation; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D034741:RNA, Small Interfering; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C077591:S100A4 protein, human