Monocarboxylate transporter 4 facilitates cell proliferation and migration and is associated with poor prognosis in oral squamous cell carcinoma patients

Jiang Zhu; Yu-Nong Wu; Wei Zhang; Xiao-Min Zhang; Xu Ding; Huai-Qi Li; Meiyu Geng; Zuo-Quan Xie; He-Ming Wu

doi:10.1371/journal.pone.0087904

Monocarboxylate transporter 4 facilitates cell proliferation and migration and is associated with poor prognosis in oral squamous cell carcinoma patients

PLoS One. 2014 Jan 30;9(1):e87904. doi: 10.1371/journal.pone.0087904. eCollection 2014.

Authors

Jiang Zhu¹, Yu-Nong Wu², Wei Zhang², Xiao-Min Zhang², Xu Ding², Huai-Qi Li², Meiyu Geng³, Zuo-Quan Xie³, He-Ming Wu¹

Affiliations

¹ Institute of Stomatology, Nanjing Medical University, Nanjing, PR China ; Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Jiangsu Province, Nanjing, PR China.
² Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Jiangsu Province, Nanjing, PR China.
³ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, China Academy of Sciences, Shanghai, China.

Abstract

Monocarboxylate transporter 4 (MCT4) is a cell membrane transporter of lactate. Recent studies have shown that MCT4 is over-expressed in various cancers; however, its role in cancer maintenance and aggressiveness has not been fully demonstrated. This study investigated the role of MCT4 in oral squamous cell carcinoma (OSCC), and found that it is highly expressed in OSCC patients by using immunohistochemistry. Moreover, this over-expression of MCT4 was closely associated with tumor size, TNM classification, lymphatic metastasis, distant metastasis and tumor recurrence, and also poor prognosis. To further study mechanisms of MCT4 in vitro, we used small-interfering RNA to silence its expression in OSCC cell lines. The results showed that knock-down of MCT4 decreased cell proliferation, migration, and invasion. The inhibition of proliferation was associated with down-regulation of p-AKT and p-ERK1/2, while decreased cell migration and invasion may be caused by down-regulation of integrin β4-SRC-FAK and MEK-ERK signaling. Together, these findings provide new insight into the critical role of MCT4 in cell proliferation and metastasis in OSCC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Squamous Cell / genetics*
Carcinoma, Squamous Cell / pathology
Cell Line, Tumor
Cell Movement / genetics*
Cell Proliferation
Down-Regulation / genetics
Female
Humans
Lymphatic Metastasis / genetics
Lymphatic Metastasis / pathology
MAP Kinase Signaling System / genetics
Male
Middle Aged
Monocarboxylic Acid Transporters / genetics*
Mouth Neoplasms / genetics*
Mouth Neoplasms / pathology
Muscle Proteins / genetics*
Neoplasm Recurrence, Local / genetics
Neoplasm Recurrence, Local / pathology
Prognosis
Proto-Oncogene Proteins c-akt / genetics

Substances

Monocarboxylic Acid Transporters
Muscle Proteins
SLC16A4 protein, human
Proto-Oncogene Proteins c-akt

Grants and funding

This work was supported by National Natural Science Foundation of China (NO. 81202549), National Science and Technology Major Project of the Ministry of Science and Technology of China (No. 2012ZX09301001-007), and by Priority Academic Program Development of Jiangsu Higher Education Institutions (No. jx10531801/005).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.