Pyruvate kinase isoenzyme M2 is a glycolytic sensor differentially regulating cell proliferation, cell size and apoptotic cell death dependent on glucose supply

Spoden, Gilles A.; Rostek, Ursula; Lechner, Stefan; Mitterberger, Michael; Mazurek, Sybille; Zwerschke, Werner

doi:10.1016/j.yexcr.2009.06.024

Cited by 88 publications

(90 citation statements)

References 52 publications

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“…Thus, it was concluded that PKM2 is crucial for cancer cell growth, to promote proliferation and to inhibit apoptosis. Based on this conclusion, the inhibition of PKM2 may elicit anticancer effects, which has been reported to involve various mechanisms, including the impairment of tumor growth, induction of apoptotic cell death and increased sensitivity to chemotherapy (7,11,25,26). In the present study, increased PKM2 expression by transfection may partially reverse the effects of PPZ in inhibiting cancer cell proliferation and inducing apoptosis.…”

Section: Discussionsupporting

confidence: 58%

Pantoprazole inhibits human gastric adenocarcinoma SGC-7901 cells by downregulating the expression of pyruvate kinase M2

et al. 2015

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Abstract. The Warburg effect is important in tumor growth. The human M2 isoform of pyruvate kinase (PKM2) is a key enzyme that regulates aerobic glycolysis in tumor cells. Recent studies have demonstrated that PKM2 is a potential target for cancer therapy. The present study investigated the effects of pantoprazole (PPZ) treatment and PKM2 transfection on human gastric adenocarcinoma SGC-7901 cells in vitro. The present study revealed that PPZ inhibited the proliferation of tumor cells, induced apoptosis and downregulated the expression of PKM2, which contributes to the current understanding of the functional association between PPZ and PKM2. In summary, PPZ may suppress tumor growth as a PKM2 protein inhibitor.

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Section: Discussionsupporting

confidence: 58%

Pantoprazole inhibits human gastric adenocarcinoma SGC-7901 cells by downregulating the expression of pyruvate kinase M2

et al. 2015

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“…So the transition of PKM2 according to cells' demand between the two conformations channels glucose carbons either into catabolic or into anabolic pathways and optimizes tumor cell proliferation, growth, and survival (29). Another contradiction to be mentioned in tumor cells is that in contrast with normal proliferating cells, tumor cells have to survive in environments with insufficient oxygen and nutrient supplies (29,30). So the expression of PKM2 induces a switch to anaerobic metabolism, which allows maintenance of metabolic activities and ATP supply in the absence of oxygen.…”

Section: Discussionmentioning

confidence: 99%

“…So the expression of PKM2 induces a switch to anaerobic metabolism, which allows maintenance of metabolic activities and ATP supply in the absence of oxygen. Recent studies (29) have indicated that an inactive dimer of PKM2 can rescue tumor cells from glucose starvation-induced apoptotic cell death and can optimize tumor cell metabolic activity, proliferation, growth, and survival by economizing the less glucose available to synthetic processes. We found that overexpression of PKM2 was correlated with later tumor stage in CRC patients, suggesting that PKM2 acts to promote tumor progression and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Pyruvate kinase type M2 is upregulated in colorectal cancer and promotes proliferation and migration of colon cancer cells

Zhou

Sun

et al. 2012

IUBMB Life

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SummaryPyruvate kinase type M2 (PKM2) has been reported to be involved in aerobic glycolysis and cell growth in various tumors. However, the expression pattern of PKM2 in colorectal cancer (CRC) and the correlation between PKM2 expression and CRC remains unclear. The aim of this study is to investigate PKM2 expression and its possible role in CRC. We found that expression of PKM2 was increased in CRC and the increased PKM2 expression was associated with later stage and lymph metastasis of the tumors. Knockdown of PKM2 suppressed the aerobic glycolysis and decreased lactate production of colon cancer RKO cells. Knockdown of PKM2 repressed proliferation and migration of the cells. Inhibition of PKM2 suppressed xenograft tumor growth of RKO cells in vivo. These results suggest that the expression of PKM2 plays a critical role in development of CRC, and it may provide a growth advantage for colon cancer cells. Thus, PKM2 might be a potential therapeutic target for CRC.2012 IUBMB IUBMB Life, 64(9): 775-782, 2012

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“…PKM2 contains an inducible nuclear translocation signal in its C-domain . It has been described that nuclear PKM2 is pro-proliferative or pro-apoptotic, depending on environmental conditions (Spoden et al, 2009). Recently, it has been found that PKM2 inhibits or promotes EMT in gastric cancer cells, depending on differentiation status of the cells (Wang et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

PKM2 Regulates Hepatocellular Carcinoma Cell Epithelial-mesenchymal Transition and Migration upon EGFR Activation

Fan

Shen²,

Li³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Pyruvate kinase isozyme type M2 (PKM2) was first found in hepatocellular carcinoma (HCC), and its expression has been thought to correlate with prognosis. A large number of studies have demonstrated that epithelial-mesenchymal transition (EMT) is a crucial event in hepatocellular carcinoma (HCC) and associated metastasis, resulting in enhanced malignancy of HCC. However, the roles of PKM2 in HCC EMT and metastasis remain largely unknown. The present study aimed to determine the effects of PKM2 in EGF-induced HCC EMT and elucidate the molecular mechanisms in vitro. Our results showed that EGF promoted EMT in HCC cell lines as evidenced by altered morphology, expression of EMT-associated markers, and enhanced invasion capacity. Furthermore, the present study also revealed that nuclear translocation of PKM2, which is regulated by the ERK pathway, regulated β-catenin-TCF/LEF-1 transcriptional activity and associated EMT in HCC cell lines. These discoveries provide evidence of novel roles of PKM2 in the progression of HCC and potential therapeutic target for advanced cases.

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Pyruvate kinase isoenzyme M2 is a glycolytic sensor differentially regulating cell proliferation, cell size and apoptotic cell death dependent on glucose supply

Cited by 88 publications

References 52 publications

Pantoprazole inhibits human gastric adenocarcinoma SGC-7901 cells by downregulating the expression of pyruvate kinase M2

Pantoprazole inhibits human gastric adenocarcinoma SGC-7901 cells by downregulating the expression of pyruvate kinase M2

Pyruvate kinase type M2 is upregulated in colorectal cancer and promotes proliferation and migration of colon cancer cells

PKM2 Regulates Hepatocellular Carcinoma Cell Epithelial-mesenchymal Transition and Migration upon EGFR Activation

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