27 June 2017 : Laboratory Research
P53 and Protein Phosphorylation Regulate the Oncogenic Role of Epithelial Cell Transforming 2 (ECT2)
Yan Chen1B, Ping Tian1C, Yi Liu2A*DOI: 10.12659/MSM.905388
Med Sci Monit 2017; 23:3154-3160
Abstract
BACKGROUND: Gastric cancer (GC) is the second leading cause of cancer-related death worldwide, but little progress has been achieved in the treatment of advanced or metastatic GC. GC is highly heterogeneous and more studies are needed to elucidate the metastatic mechanisms. Epithelial cell transforming 2 (ECT2) has been reported to be up-regulated in GC tissues, but its signaling mechanisms remain unclear.
MATERIAL AND METHODS: In this study, we used Western blot analysis to compare the expression level of ECT2 in 2 GC cell lines: MKN1 and MKN45. Mutagenesis and transfections were conducted to investigate the oncogenic mechanisms of ECT2 in GC cells.
RESULTS: ECT2 was expressed at higher levels in MKN1 than in MKN45. Immunoblotting results showed that MKN1 expression was suppressed by p53-WT but was enhanced by p53-mutant. In addition, in vitro experiments showed that ECT2 positively regulated the proliferation and invasion of GC cells. To better explore the mechanisms of ECT2 in promoting GC progression, we introduced site-directed mutants of ECT2, and found that the phosphor-mimic mutant T359D enhanced its oncogenic activity. In contrast, activation of RhoA was inhibited in cells transfected with ECT2 phosphor-deficient mutant T359A. We found that the epithelial cell biomarker E-cadherin was down-regulated by ECT2-T359D, highlighting the role of phosphorylation in regulating epithelial-mesenchymal transition.
CONCLUSIONS: Our results identified p53 as a novel up-stream signaling molecule of ECT2 in GC cells, and the post-translational modifications of ECT2 play important roles in regulating cancer development and progression.
Keywords: Phosphorylation, Tumor Suppressor Protein p53
Editorial
01 April 2024 : Editorial
Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug ResistanceDOI: 10.12659/MSM.944600
Med Sci Monit 2024; 30:e944600
In Press
07 Mar 2024 : Clinical Research
Knowledge of and Attitudes Toward Clinical Trials: A Questionnaire-Based Study of 179 Male Third- and Fourt...Med Sci Monit In Press; DOI: 10.12659/MSM.943468
08 Mar 2024 : Animal Research
Modification of Experimental Model of Necrotizing Enterocolitis (NEC) in Rat Pups by Single Exposure to Hyp...Med Sci Monit In Press; DOI: 10.12659/MSM.943443
18 Apr 2024 : Clinical Research
Comparative Analysis of Open and Closed Sphincterotomy for the Treatment of Chronic Anal Fissure: Safety an...Med Sci Monit In Press; DOI: 10.12659/MSM.944127
08 Mar 2024 : Laboratory Research
Evaluation of Retentive Strength of 50 Endodontically-Treated Single-Rooted Mandibular Second Premolars Res...Med Sci Monit In Press; DOI: 10.12659/MSM.944110
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952