RRC ID 44060
Author Kim SH, Jang YH, Chau GC, Pyo S, Um SH.
Title Prognostic significance and function of phosphorylated ribosomal protein S6 in esophageal squamous cell carcinoma.
Journal Mod Pathol
Abstract Ribosomal protein S6 is a key regulator of 40S ribosome biogenesis, and its phosphorylation is closely related to cell growth capacity. However, as a downstream target of S6 kinases, the clinical significance and the roles of S6 and S6 phosphorylation in cell viability and motility of esophageal squamous cell carcinoma remain unclear. Here, we show that high level of phosphorylated-ribosomal protein S6 (p-S6) (immunohistochemistry score ≥5) and an increased ratio of p-S6/S6 (immunohistochemistry score ≥0.75) were significantly associated with shortened disease-free survival in patients with esophageal squamous cell carcinoma in univariate analysis (P=0.049 and P<0.001, respectively). After adjusting for age, tumor-nodes-metastasis stage, chemotherapy, and radiation therapy in multivariate analysis, both p-S6 (hazard ratio 2.21, P=0.005) and p-S6/S6 (hazard ratio 2.40, P<0.001) remained independent adverse prognostic factors. In addition, S6 and S6 kinase 1 knockdown resulted in attenuation of viability by suppressing cyclin D1 expression in esophageal cancer cells. Furthermore, depletion of S6 and S6 kinase 1 resulted in a reduction in esophageal cancer cell migration and invasion. This was paralleled by a reduction in focal adhesion and by suppression of extracellular signal-regulated kinase and c-jun N-terminal kinase phosphorylation, which control cell motility. Collectively, these findings suggest that p-S6 and the ratio of p-S6/S6 are closely relevant to tumor progression and have prognostic significance in esophageal squamous cell carcinoma.
Volume 26(3)
Pages 327-35
Published 2013-3-1
DOI 10.1038/modpathol.2012.161
PII modpathol2012161
PMID 22996377
MeSH Aged Carcinoma, Squamous Cell / enzymology* Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / mortality Carcinoma, Squamous Cell / pathology Carcinoma, Squamous Cell / therapy Cell Line, Tumor Cell Movement Cell Survival Cyclin D1 / metabolism Disease-Free Survival Esophageal Neoplasms / enzymology* Esophageal Neoplasms / genetics Esophageal Neoplasms / mortality Esophageal Neoplasms / pathology Esophageal Neoplasms / therapy Extracellular Signal-Regulated MAP Kinases / metabolism Female Focal Adhesions / enzymology Humans Immunohistochemistry JNK Mitogen-Activated Protein Kinases / metabolism Kaplan-Meier Estimate Male Middle Aged Multivariate Analysis Neoplasm Invasiveness Phosphorylation Prognosis Proportional Hazards Models RNA Interference Ribosomal Protein S6 / genetics Ribosomal Protein S6 / metabolism* Ribosomal Protein S6 Kinases / metabolism Risk Assessment Risk Factors Time Factors Transfection
IF 6.365
Times Cited 26
Human and Animal Cells