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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MDPI AG
2020-07-01
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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. |
first_indexed | 2024-03-10T18:06:55Z |
format | Article |
id | doaj.art-4f3d9db1a4e04553b457d35cbe909849 |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-10T18:06:55Z |
publishDate | 2020-07-01 |
publisher | MDPI AG |
record_format | Article |
series | International Journal of Molecular Sciences |
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 |
work_keys_str_mv | AT miyakokuriharashimomura peroxidanplaysatumorpromotingroleinoralsquamouscellcarcinoma AT tomonorisasahira peroxidanplaysatumorpromotingroleinoralsquamouscellcarcinoma AT hiroyukishimomura peroxidanplaysatumorpromotingroleinoralsquamouscellcarcinoma AT tadaakikirita peroxidanplaysatumorpromotingroleinoralsquamouscellcarcinoma |