The Effect of Fructose-bisphosphate Aldolase C in Oral Squamous Cell Carcinoma Progression
Date Issued
2014
Date
2014
Author(s)
Huang, Tse-Hung
Abstract
Objectives:
Glycolysis machinery regulates cancer cell behavior. However, the role of these glycolysis enzyme in oral squamous cell carcinoma (OSCC) progression is still largely unknown.
Materials and Methods:
Fructose-bisphosphate aldolase C (ALDOC) expression in OSCC patients and cell lines was detected by real-time quantitative RT-PCR. The functions of ALDOC in migration and invasion ability of OSCC cells were determined by gain and loss function approaches. The orthotopic OSCC animal model was performed to investigate the effects of ALDOC on OSCC cell lymph node metastasis and tumorigensis in vivo.
Results:
ALDOC mRNA and protein expression was significantly decreased in advanced migratory cells including SAS and Ca9-22 cells. Clinical data revealed that ALDOC mRNA expression negatively correlated with lymph node metastasis and advanced tumor TNM stage in 68 OSCC patients. Overexpressed ALDOC block ATP generation and lactate production resulted in cell motility retardation. Transfected silenced ALDOC expression plasmid could restore OSCC cell migration and invasion.
Furthermore, Transfection of ALDOC point mutation constructs of catalytic domain, Arg42 and K146 in SAS cells could functionally restore the ALDOC-inhibited cell migration and invasion. In vivo, ALDOC overexpressed significantly decreased lymph node metastasis and prolong mice survival.
Conclusion:
ALDOC plays as an OSCC prognosis marker clinically, and functions to suppressor OSCC cell migration and invasion, and the catalytic domain of Arg42 and K146 is crucial in this regulations machinery. ALDOC could be a potential therapeutic target to block OSCC progression.
Subjects
口腔癌
轉移
果糖二磷酸醛縮酶C
糖解酶
代謝
SDGs
Type
other
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