Abstract
Pyruvate kinase M2 (PKM2) is a key kinase of glycolysis and is characteristic of all proliferating cells. The role of PKM2 in gastric cancer (GC) is still ambiguous and yet to be determined. To better understand the role of PKM2 in both the migration and invasion of GC, we measured the expression of PKM2 in GC cell lines using qRT-PCR and western blot. The prognostic value of PKM2 was analyzed by Immunohistochemistry in a cohort containing 88 GC patients. PKM2 was knocked down by the short hairpin RNA plasmid vector in NCI-N87 and BGC-823 cells, and the biological behavior and downstream signaling pathways were also investigated in vitro. Subcutaneous xenografts and pulmonary metastases models were constructed in nude mice to compare the differences in tumorgenesis and metastasis after Knockdown of PKM2. Our results obtained from in vitro cell biological behavior, in vivo tumorigenicity studies, and primary GC samples revealed an oncogenic role for PKM2 in GC. Furthermore, for those GC patients who received radical resection, PKM2 might serve as a novel prognostic biomarker and target which would allow for a brand new treatment strategy for GC in the clinical settings.
Highlights
Gastric cancer (GC) is one of the most common malignancies worldwide and occurs at a highest frequency in Eastern Asia, especially in China[1]
Pyruvate kinase isoform M2 (PKM2) shRNA treatment suppressed the growth of NCI-N87 cells (P < 0.0001; Fig. 2F); what we found reconfirmed that PKM2 promotes the growth of gastric cancer (GC) cells[15]
We demonstrated that the expression of PKM2 is higher in GC tissues as compared to adjacent normal gastric tissues
Summary
Gastric cancer (GC) is one of the most common malignancies worldwide and occurs at a highest frequency in Eastern Asia, especially in China[1]. Proliferative activity and relative poor prognosis in GC have been shown to correlate directly with PKM2 expression, especially in signet ring cell gastric cancer[14, 15], the exact role of PKM2 in GC and the mechanism by which it exerts its oncogenic role, is yet to be determined. We investigated the expression of PKM2 in clinical GC samples and observed a correlation between PKM2 expression and poor clinical outcome of GC patients. Such a correlation was further confirmed in GC cell lines both in vivo and in vitro. We identified PKM2 as an upstream regulator of PI3K/AKT (phosphatidylinositol 3-kinase/AKT) oncogenic pathway in GC, which can mediate both migration and autophagy
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