Monocarboxylate transporter 4 facilitates cell proliferation and migration and is associated with poor prognosis in oral squamous cell carcinoma patients.
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.
Institute of Stomatology, Nanjing Medical University, Nanjing, PR China ; Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Jiangsu Province, Nanjing, PR China.
Jiang
J
Zhu
Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Jiangsu Province, Nanjing, PR China.
Yu-Nong
YN
Wu
Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Jiangsu Province, Nanjing, PR China.
Wei
W
Zhang
Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Jiangsu Province, Nanjing, PR China.
Xiao-Min
XM
Zhang
Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Jiangsu Province, Nanjing, PR China.
Xu
X
Ding
Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Jiangsu Province, Nanjing, PR China.
Huai-Qi
HQ
Li
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, China Academy of Sciences, Shanghai, China.
Meiyu
M
Geng
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, China Academy of Sciences, Shanghai, China.
Zuo-Quan
ZQ
Xie
Institute of Stomatology, Nanjing Medical University, Nanjing, PR China ; Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Jiangsu Province, Nanjing, PR China.
He-Ming
HM
Wu
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000235:genetics*; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D009124:Muscle Proteins / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics
D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; C406962:SLC16A4 protein, human; D051057:Proto-Oncogene Proteins c-akt