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

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 (<i>PXDN<...

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Main Authors: Miyako Kurihara-Shimomura, Tomonori Sasahira, Hiroyuki Shimomura, Tadaaki Kirita
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/15/5416
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author Miyako Kurihara-Shimomura
Tomonori Sasahira
Hiroyuki Shimomura
Tadaaki Kirita
author_facet Miyako Kurihara-Shimomura
Tomonori Sasahira
Hiroyuki Shimomura
Tadaaki Kirita
author_sort Miyako Kurihara-Shimomura
collection DOAJ
description 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 (<i>PXDN</i>) 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.
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spelling doaj.art-4f3d9db1a4e04553b457d35cbe9098492023-11-20T08:26:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-012115541610.3390/ijms21155416Peroxidan Plays a Tumor-Promoting Role in Oral Squamous Cell CarcinomaMiyako Kurihara-Shimomura0Tomonori Sasahira1Hiroyuki Shimomura2Tadaaki Kirita3Department of Oral and Maxillofacial Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, JapanDepartment of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, JapanDepartment of Oral and Maxillofacial Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, JapanDepartment of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, JapanDespite 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 (<i>PXDN</i>) 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.https://www.mdpi.com/1422-0067/21/15/5416oral cancerPXDNnodal metastasisinvasionprognosis
spellingShingle Miyako Kurihara-Shimomura
Tomonori Sasahira
Hiroyuki Shimomura
Tadaaki Kirita
Peroxidan Plays a Tumor-Promoting Role in Oral Squamous Cell Carcinoma
International Journal of Molecular Sciences
oral cancer
PXDN
nodal metastasis
invasion
prognosis
title Peroxidan Plays a Tumor-Promoting Role in Oral Squamous Cell Carcinoma
title_full Peroxidan Plays a Tumor-Promoting Role in Oral Squamous Cell Carcinoma
title_fullStr Peroxidan Plays a Tumor-Promoting Role in Oral Squamous Cell Carcinoma
title_full_unstemmed Peroxidan Plays a Tumor-Promoting Role in Oral Squamous Cell Carcinoma
title_short Peroxidan Plays a Tumor-Promoting Role in Oral Squamous Cell Carcinoma
title_sort peroxidan plays a tumor promoting role in oral squamous cell carcinoma
topic oral cancer
PXDN
nodal metastasis
invasion
prognosis
url https://www.mdpi.com/1422-0067/21/15/5416
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AT tomonorisasahira peroxidanplaysatumorpromotingroleinoralsquamouscellcarcinoma
AT hiroyukishimomura peroxidanplaysatumorpromotingroleinoralsquamouscellcarcinoma
AT tadaakikirita peroxidanplaysatumorpromotingroleinoralsquamouscellcarcinoma