Aberrant Overexpression of Pyruvate Kinase M2 Is Associated With Aggressive Tumor Features and the BRAF Mutation in Papillary Thyroid Cancer

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Abstract

Context:

Many tumor cells predominantly generate energy through high rates of glycolysis. Pyruvate kinase M2 (PKM2) has been identified as being necessary for aerobic glycolysis.

Objective:

The aim of this study was to investigate the expression pattern of PKM2 in papillary thyroid cancer (PTC) and the possible role of PKM2 in PTC.

Design:

The expression of PKM2 in human thyroid tissues was examined using immunocytochemistry. PKM2 expression in PTC correlated with clinicopathological features and the BRAF mutation. PTC cells were transfected with small interfering RNA against PKM2. PKM2 expression in cells was analyzed by Western blotting and real-time RT-PCR. Cell growth was evaluated both in vitro and in vivo. Lactate and ATP production and glucose consumption by cells were determined using commercial assay kits.

Results:

PKM2 was aberrantly overexpressed in PTC. This overexpression was associated with poor clinicopathological features including advanced tumor stages and lymph node metastasis. More intensive immunostaining of PKM2 was detected in PTCs harboring the BRAF mutation. Specific small interfering RNA against PKM2 in PTC cell lines retarded cell growth both in vitro and in xenograft mouse models. PKM2 knockdown also reduced lactate and ATP production and glucose consumption by PTC cells.

Conclusions:

We conclude that overexpression of PKM2 provides a selective growth advantage for PTC cells through activation of glycolysis. Aberrant PKM2 overexpression may serve as a novel biomarker and a potential treatment target for PTC. The BRAF mutation may contribute to alterations in the expression pattern of glycolytic enzymes such as PKM2.

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