Peroxidan Plays a Tumor-Promoting Role in Oral Squamous Cell Carcinoma.

Miyako Kurihara-Shimomura,Hiroyuki Shimomura,Tadaaki Kirita,Tomonori Sasahira

doi:10.3390/ijms21155416

Miyako Kurihara-Shimomura, Hiroyuki Shimomura + Show 2 more

Open Access

https://doi.org/10.3390/ijms21155416

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Abstract

Despite dramatic progress in cancer diagnosis and treatment, the five-year survival rate of oral squamous cell carcinoma (OSCC) is still only about 50%. Thus, the need for elucidating the molecular mechanisms underlying OSCC is urgent. We previously identified the peroxidasin gene (PXDN) as one of several novel genes associated with OSCC. Although the PXDN protein is known to act as a tumor-promoting factor associated with the Warburg effect, its function and role in OSCC are poorly understood. In this study, we investigated the expression, function, and relationship with the Warburg effect of PXDN in OSCC. In immunohistochemical analysis of OSCC specimens, we observed that elevated PXDN expression correlated with lymph node metastasis and a diffuse invasion pattern. High PXDN expression was confirmed as an independent predictor of poor prognosis by multivariate analysis. The PXDN expression level correlated positively with that of pyruvate kinase (PKM2) and heme oxygenase-1 (HMOX1) and with lactate and ATP production. No relationship between PXDN expression and mitochondrial activation was observed, and PXDN expression correlated inversely with reactive oxygen species (ROS) production. These results suggest that PXDN might be a tumor progression factor causing a Warburg-like effect in OSCC.

Highlights

Oral squamous cell carcinoma (OSCC) is a highly aggressive tumor, with 355,000 new cases and 177,000 deaths worldwide predicted in 2018 [1]
Tissue samples from 111 OSCC patients were immunohistochemically stained for PXDN expression
PXDN expression in OSCC was a significant influence on the mode of invasion based on the pattern of invasion (POI) (p = 0.0307) [19,20,21]

Summary

Introduction

Oral squamous cell carcinoma (OSCC) is a highly aggressive tumor, with 355,000 new cases and 177,000 deaths worldwide predicted in 2018 [1]. Despite remarkable advances in the treatment of OSCC and increases in our understanding of its molecular biology, five-year survival rates over the past three decades have remained at approximately 50% [3]. Further elucidation of the molecular mechanisms underlying OSCC is needed. We previously identified several candidate genes involved in the progression of OSCC using cDNA microarray [4]. Among the overexpressed candidate genes is the extracellular matrix (ECM) protein peroxidasin (PXDN). This protein belongs to a family of heme-containing peroxidases that catalyze the production of reactive oxygen species (ROS), including hydrogen peroxide [5,6]. PXDN is associated with poor prognosis and promotes cell proliferation, invasion, and migration through activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway [11]

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