@Article{096504017X14886420642823,
AUTHOR = {Ping Wu, Huatao Quan, Jing Kang, Jian He, Shi Luo, Chubo Xie, Jing Xu, Yaoyun Tang, Suping Zhao},
TITLE = {Downregulation of Calcium-Binding Protein S100A9 Inhibits  Hypopharyngeal Cancer Cell Proliferation and Invasion  Ability Through Inactivation of NF-κB Signaling},
JOURNAL = {Oncology Research},
VOLUME = {25},
YEAR = {2017},
NUMBER = {9},
PAGES = {1479--1488},
URL = {http://www.techscience.com/or/v25n9/56933},
ISSN = {1555-3906},
ABSTRACT = {Hypopharyngeal cancer (HPC) frequently presents at an advanced stage and displays early submucosal spread, 
resulting in a poor prognosis. It is among the worst of all cancers in the head and neck subsites. Therefore, 
detection of HPC at an earlier stage would be beneficial to patients. In this study, we used differential in-gel 
electrophoresis (DIGE) and two-dimensional polyacrylamide gel electrophoresis (2-DE) proteomics analysis 
to identify the potential biomarkers for HPC. Among the differential proteins identified, calcium-binding protein S100A9 was overexpressed in HPC tissues compared with normal adjacent tissues, and S100A9 expression in metastatic tissues and advanced tumor tissues was higher than in nonmetastatic tissues and early tumor 
tissues. S100A9 expression was further confirmed in a large additional cohort. Our data showed that a higher 
S100A9 level was associated with a poor prognosis for HPC patients, and this may be an independent factor 
for predicting their prognosis. In addition, S100A9 protein expression was upregulated in human HPC cell 
lines compared with normal oral cavity epithelia. Knockdown of S100A9 induced significant inhibition of cell 
growth and their invasive ability. Mechanically, we found that downregulation of S100A9 significantly reduced 
the expression of NF-kB, phosphorylation of NF-kB and Bcl-2, as well as the expression of MMP7 and MMP2. 
Restoration of NF-kB expression sufficiently reversed the inhibitory effects on cell proliferation and invasion 
induced by S100A9 downregulation in vitro and in vivo. In conclusion, for the first time, we have identified 
S100A9 as an independent prognostic factor for HPC. Inhibiting S100A9 expression would be a potential novel 
diagnostic biomarker and therapeutic target for HPC treatment.},
DOI = {10.3727/096504017X14886420642823}
}