p53 Attenuates the oncogenic Ras-induced epithelial–mesenchymal transition in human mammary epithelial cells

• Published in: Biochemical and biophysical research communications Vol. 434; no. 3; pp. 606 - 613
• Main Authors: Zhang, Jianchao, Lei, Yang, Gao, Xiaoge, Liang, Qian, Li, Lili, Feng, Jingxin, Hou, Pingfu, Han, Liping, Zhang, Yu, Huang, Baiqu, Lu, Jun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.05.2013
• Subjects: Animals; Base Sequence; DNA Primers; EMT; Epithelial-Mesenchymal Transition; Flow Cytometry; Fluorescent Antibody Technique; Gene Silencing; Genes, ras; Humans; Mammary Glands, Human - cytology; MAP Kinase Signaling System; Mice; p53; Ras; Stem cell; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - physiology; Ras; EMT; Stem cell; p53
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2013.03.124

•Increased expression of p53 reversed the EMT phenotype.•Restoration of p53 expression suppressed EMT-mediated stem cell phenotype.•Enhanced expression of p53 reduced the oncogenic Ras-induced tumor growth of human mammary epithelial cells.•p53 downregulated the oncogenic Ras-induced signaling pathways. Inactivation of the tumor suppressor p53 and activation of the oncogene Ras are the two most pivotal events in tumor development. However, potential intersection between p53 and Ras activity during an EMT process, which plays a crucial role during malignant tumor progression, remains elusive. Here, we report that increased expression of wild type p53 suppressed H-RasV12-induced EMT phenotypes and restrained stem cell properties, through downregulation of MEK-ERK signaling pathways. In vivo experiments showed that p53 was able to inhibit H-RasV12-induced tumor growth of human mammary epithelial cells. This study elucidates a novel correlation between the tumor suppressor gene p53 and the oncogene Ras in regulating EMT program, and expands the knowledge about the function of p53 in EMT process.