1. p53R2 overexpression in cervical cancer promotes AKT signaling and EMT, and is correlated with tumor progression, metastasis and poor prognosis
- Author
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Mei Yin Zhang, Ju Deng Zeng, Hui-Yun Wang, Xiao Yi Xu, Yang Yang, Xiao Xing Li, Wen Qian Liang, Chao Jiang, Yan Yan Wang, Rui Xu, X. F.Steven Zheng, and Shanshan Zhang
- Subjects
0301 basic medicine ,Epithelial-Mesenchymal Transition ,DNA repair ,Down-Regulation ,Uterine Cervical Neoplasms ,Cell Cycle Proteins ,Kaplan-Meier Estimate ,Biology ,Metastasis ,Cell Cycle News & Views ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Cell Movement ,Cell Line, Tumor ,Ribonucleotide Reductases ,medicine ,Humans ,Neoplasm Invasiveness ,Epithelial–mesenchymal transition ,Neoplasm Metastasis ,Molecular Biology ,Protein kinase B ,Cell Proliferation ,Cervical cancer ,Cell growth ,Cell Biology ,Middle Aged ,Prognosis ,medicine.disease ,Immunohistochemistry ,Survival Analysis ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Tumor progression ,030220 oncology & carcinogenesis ,Multivariate Analysis ,Immunology ,Disease Progression ,Cancer research ,Female ,Proto-Oncogene Proteins c-akt ,Signal Transduction ,Developmental Biology - Abstract
p53R2 is a p53-inducible ribonucleotide reductase subunit involved in deoxyribonucleotide biosynthesis and DNA repair. Although p53R2 has been linked to human cancer, its role in cervical cancer remains unknown. In this study, we investigated the expression and clinical significance of p53R2 in early-stage cervical cancer. p53R2 expression is significantly upregulated at both mRNA and protein levels in cervical cancer cells and tissues, compared with that in matched normal cervical cells and tissues, respectively. p53R2 overexpression is associated with increased risk of pelvic lymph node metastasis (PLNM, p = 0.001) and cancer relapse (p = 0.009). Patients with high p53R2 expression have a shorter overall survival (OS) and disease-free survival (DFS). p53R2 is an independent factor for predicting OS and DFS of cervical cancer patients. We further show that p53R2 is important for oncogenic growth, migration and invasion in cervical cancer cells. Mechanistically, p53R2 promotes Akt signaling and epithelial-mesenchymal transition (EMT). In conclusion, our study demonstrates for the first time that p53R2 protein is overexpressed in early-stage cervical cancer and unravels some unconventional oncogenic functions of p53R2. p53R2 may be a useful prognostic biomarker and therapeutic target for cervical cancer.
- Published
- 2017