Abstract
Pyruvate kinase M2 (PKM2) is a member of the pyruvate kinase family. Recent work has defined the "non-metabolic" functions of PKM2. However, the role of PKM2 in HCC remains unclear. To investigate the role of PKM2 in tumor growth, invasion and the prognosis of hepatocellular carcinoma (HCC), PKM2 expression was measured in HCC cell lines and tissues using qRT-PCR, western blot, and immunofluorescence assays. In in vitro experiments, PKM2 was knocked down using a short hairpin RNA lentivirus vector, and tumor cell behavior and the downstream signaling pathways and chemokine were analyzed. For the analysis of in vivo tumor growth, intratumoral and peritumoral lymphocyte infiltration were examined in nude mice. The prognostic value of PKM2 was analyzed by immunohistochemistry in two cohorts including 721 HCC patients. Together, our data obtained from cell lines, tumorigenicity studies, and primary HCC samples illustrate an oncogenic role for PKM2 in tumors. Moreover, PKM2 may serve as a novel prognostic indicator for HCC patients after curative resection, targeted therapy aimed at PKM2 may represent an effective treatment approach for HCC.
Highlights
Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death worldwide, and the burden of this disease is especially high in developing countries [1]
We examined Pyruvate kinase M2 (PKM2) expression in a series of hepatocellular carcinoma (HCC) cell lines with increasing metastatic potential (L02, Hep3B, HepG2, SMMC-7721, Huh7, HCC97L, HCC-97H, and HCCLM3)
The trend of increased PKM2 mRNA and protein expression in cancer cells was consistent with the metastatic potential (Fig. 1B, 1C)
Summary
Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death worldwide, and the burden of this disease is especially high in developing countries [1]. Significant HCC research has focused on oncogenes and tumor suppressor genes, the importance of cancer cell metabolism has been recently highlighted [2]. Cancer cell metabolism is known as the Warburg effect [3, 4], whereby cancer cells shift their glucose metabolism largely to glycolysis via a process called “aerobic glycolysis.”. PK converts phosphoenolpyruvate (PEP) and ADP to pyruvate and ATP and regulates glucose carbon flux in the cell [5]. Types L and R are expressed in the liver and erythrocytes; type M1 is present in most normal tissue; and type M2 is characteristic of all proliferating cells, especially tumor cells [6]. PKM1 and PKM2 represent different splicing products of the same mRNA transcript, but they differ in terms of 21 amino acids [7]
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