Downregulation of Calcium Binding Protein S100A9 Inhibits Hypopharyngeal Cancer Cell Proliferation and Invasion Ability Through Inactivation of NFκB Signaling.

Downregulation of Calcium Binding Protein S100A9 Inhibits Hypopharyngeal Cancer Cell Proliferation and Invasion Ability Through Inactivation of NFκB Signaling.

Oncol Res. 2017 Mar 08;:

Authors: Wu P, Quan H, Kang J, He J, Luo S, Xie C, Xu J, Tang Y, Zhao S

Abstract
Hypopharyngeal cancer (HPC) frequently present at an advanced stage, and display early submucosal spread, resulting inpoor prognosis, among the worst of all head and neck subsites. 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 indentify 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 non-metastatic tissues and early tumor tissues, respectively. S100A9 expression was further confirmed in a large additional cohort. Our data showed that higher S100A9 level was associated with poor prognosis of HPC patients, which may be an independent factor for predicating the prognosis of HPC patients. In addition, S100A9 protein expression also upregulated in human hypopharyngeal cancer cell lines compared with normal oral cavity epithelia. And knockdown of S100A9 induced significant inhibition on cell growth and invasion ability. Mechanically, we found that downregulation of S100A9 significantly reduced the expression of NFκB, phosphorylation of NFκB and Bcl-2, as well as the expression of MMP7 and MMP2. And restoration of NFκB expression sufficiently reversed the inhibitory effects on cell proliferation and invasion induced by S100A9 downregulation in vitro and in vivo. In conclusion, we first time indentify S100A9 as an independent prognostic factor for HPC. And inhibiting S100A9 expression would be a novel potential diagnostic biomarker and therapeutic target for HPC treatment.

PMID: 28276321 [PubMed - as supplied by publisher]

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