Nuclear PKM2 expression predicts poor prognosis in patients with esophageal squamous cell carcinoma

Zhang, Xuelin; He, Chengzhi; Chun-ya, HE; Chen, Baofu; Liu, Yanxia; Kong, Min; Wang, Chunguo; Lin, Lizhong; Dong, Yan; Sheng, Haihui

doi:10.1016/j.prp.2013.06.005

Cited by 44 publications

(30 citation statements)

References 47 publications

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“…Indeed, nuclear PKM2 has been suggested to be a poor prognosticator for certain head and neck SCCs (87). Four isozymes of PDK are described to date.…”

Section: Discussionmentioning

confidence: 99%

Monoallelic loss of tumor suppressor GRIM-19 promotes tumorigenesis in mice

Kalakonda¹,

Nallar²,

Jaber

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Significance Gene-associated with retinoid-interferon induced mortality-19 (GRIM-19) is an interferon-retinoid–regulated growth suppressor that inhibits cell growth by targeting the transcription factor STAT3 for inhibition. In primary human tumors GRIM-19 is suppressed or mutated, leading to constitutive STAT3 activity and indicating the tumor-suppressive function of GRIM-19. To understand the in vivo role of Grim-19 in tumor development, we generated a Grim-19 conditional knockout mouse. We found that deletion of even a single Grim-19 allele is sufficient to augment skin tumorigenesis in mice, thus establishing a critical role for Grim-19 as a tumor suppressor. Tumors that developed in the absence of Grim-19 exhibited mitochondrial respiratory chain dysfunction, elevated glycolysis, and Stat3-responsive gene expression.

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“…Indeed, nuclear PKM2 has been suggested to be a poor prognosticator for certain head and neck SCCs (87). Four isozymes of PDK are described to date.…”

Section: Discussionmentioning

confidence: 99%

Monoallelic loss of tumor suppressor GRIM-19 promotes tumorigenesis in mice

Kalakonda¹,

Nallar²,

Jaber

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Recently, accumulating evidence has suggested that PKM2 is more than a regulator of metabolic reprogramming, suggestive of multiple non-metabolic functions during carcinogenesis. Enhanced expression of PKM2 has been reported in multiple cancers including gastric cancers [5, 6], hepatocellular carcinoma [7], esophageal squamous cell carcinoma [8, 9], colorectal cancer [10], and gallbladder cancer [11]. In addition, more recently, quite a few studies have investigated the correlation between the expression of PKM2 and prognosis among multiple cancer patients.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, more recently, quite a few studies have investigated the correlation between the expression of PKM2 and prognosis among multiple cancer patients. An overwhelming majority of evidence has explored an unfavorable prognostic value of PKM2 over-expression in a wide spectrum of cancers [8, 11–13], however, due to variance in tumor type, study design and sample size, several studies failed to draw similar conclusions. Lockney et al [14] reported that positive PKM2 expression predicted improved overall survival in pancreatic ductal adenocarcinoma patients.…”

Section: Introductionmentioning

confidence: 99%

Pyruvate kinase M2 (PKM2) expression correlates with prognosis in solid cancers: a meta-analysis

et al. 2016

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Pyruvate kinase M2 (PKM2) is the key enzyme in the Warburg effect and plays a central role in cancer cell metabolic reprogramming. Recently, quite a few studies have investigated the correlation between PKM2 expression and prognosis in multiple cancer patients, but results were inconsistent. We therefore performed a meta-analysis to explore the prognostic value of PKM2 expression in patients with solid cancer. Here twenty-seven individual studies from 25 publications with a total of 4796 cases were included to explore the association between PKM2 and overall survival (OS) or disease-free survival (DFS)/ progression-free survival (PFS)/ recurrent-free survival (RFS) in subjects with solid cancer. Pooled analysis showed that high levels of PKM2 was significantly associated with a poorer overall survival (HR = 1.73; 95%CI = 1.48-2.03) and DFS/ PFS/ RFS (HR = 1.90; 95%CI = 1.39-2.59) irrespective of cancer types. Different analysis models (univariate or multivariate models), sample-sizes (≤100 or >100), and methods for data collection (direct extraction or indirect extraction) had no impact on the negative prognostic effect of PKM2 over-expression. Nevertheless, stratified by cancer type, high-expression of PKM2 was associated with an unfavorable OS in breast cancer, esophageal squamous carcinoma, hepatocellular carcinoma and gallbladder cancer; whereas was not correlated with a worse OS in pancreatic cancer and gastric cancer. In conclusion, over-expression of PKM2 is associated with poor prognosis in most solid cancers and it might be a potentially useful biomarker for predicting cancer prognosis in future clinical applications.

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“…Zhang et al . showed that high PKM2 expression was associated with shorter overall survival in esophageal squamous cell cancer [6]. Recently, up-regulation of PKM2 in hepatocellular carcinoma has been recently reported [7, 8].…”

Section: Introductionmentioning

confidence: 99%

Pyruvate kinase M2 prevents apoptosis via modulating Bim stability and associates with poor outcome in hepatocellular carcinoma

et al. 2015

Oncotarget

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Pyruvate kinase M2 (PKM2) contributes to the Warburg effect, a hallmark of cancer. We showed that PKM2 levels were correlated with overall survival (hazard ration = 1.675, 95% confidence interval: 1.389–2.019, P < 0.001) and disease-free survival (hazard ration = 1.573, 95% confidence interval: 1.214–2.038, P < 0.001) in a cohort of 490 patients with HCC. The correlations were further validated in an independent cohort of 148 HCC patients. Multivariate analyses revealed that PKM2 was an independent indicator of poor outcome in HCC. The knockdown of PKM2 in HCC cells inhibited cell proliferation and induced apoptosis in vitro and in vivo. Bim siRNA markedly abolished the PKM2-depletion-induced apoptosis. PKM2 depletion decreased the degradation of Bim. In clinical samples, PKM2 expression was reversely correlated with Bim expression. Combination of PKM2 and Bim levels had the best prognostic significance. We suggest that PKM2 serves as a promising biomarker for poor prognosis of patients with HCC and its knockdown induces HCC apoptosis by stabilizing Bim.

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Nuclear PKM2 expression predicts poor prognosis in patients with esophageal squamous cell carcinoma

Cited by 44 publications

References 47 publications

Monoallelic loss of tumor suppressor GRIM-19 promotes tumorigenesis in mice

Monoallelic loss of tumor suppressor GRIM-19 promotes tumorigenesis in mice

Pyruvate kinase M2 (PKM2) expression correlates with prognosis in solid cancers: a meta-analysis

Pyruvate kinase M2 prevents apoptosis via modulating Bim stability and associates with poor outcome in hepatocellular carcinoma

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