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

Hu, Wen; Lu, Shi Xun; Li, Min; Zhang, Chao; Liu, Li Li; Fu, Jia; Jin, Jie; Luo, Rong; Zhang, Chris Zhiyi; Yun, Jing Ping

doi:10.18632/oncotarget.3262

Cited by 37 publications

(29 citation statements)

References 34 publications

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“…Recent evidence revealed PKM2 prevented cell apoptosis via modulating Bim stability in hepatocellular carcinoma. 46 Here we observed PKM2 also expressed in neurons, although expression changes in neurons were not evident. Whether PKM2 could inhibit neurons apoptosis after spinal cord injury should be further explored.…”

Section: Discussionmentioning

confidence: 51%

Nuclear translocation of PKM2 modulates astrocyte proliferation via p27 and β-catenin pathway after spinal cord injury

et al. 2015

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Department of Stomatology; Affiliated Hospital of Nantong University, Nantong; Nantong University; 226001, Nantong, Jiangsu, PR China y These authors equally contributed to this work, and should be considered as joint first authors.Keywords: astrocyte proliferation, b-catenin, p27, PKM2, spinal cord injuryAbbreviations: CNS, Central nervous system; CDKs, cyclin-dependent kinases; CAK, CDK activating kinase; E2F, E2 promoter-binding protein dimerization partners; GFAP, Glial fibrillary acidic protein; GAPDH, Glyceraldehyde-3-phosphate dehydrogenase; NeuN, Neuronal nuclei; PCNA, Proliferating cell nuclear antigen; PEP, phosphoenolpyruvate; PK, Pyruvate kinase; PKM2, pyruvate kinase M2; pRb, protein retinoblastoma; SCI, Spinal cord injury; EGFR, Epidermal growth factor receptor.Aberrant functionality of the cell cycle has been implicated in the pathology of traumatic SCI. Although it has been reported that the expressions of various cell cycle related proteins were altered significantly following SCI, detailed information on the subject remains largely unclear. The embryonic pyruvate kinase M2 (PKM2) is an important metabolic kinase in aerobic glycolysis or the warburg effect, however, its functions in central nervous system (CNS) injury remains elusive. Here we demonstrate that PKM2 was not only significantly upregulated by western blot and immunohistochemistry but certain traumatic stimuli also induced translocation of PKM2 into the nucleus in astrocytes following spinal cord injury (SCI). Furthermore, the expression levels and localization of p-b-catenin, p27, cyclin D1 and PCNA were correlated with PKM2 after SCI. In vitro, we also found that PKM2 co-immunoprecipitation with p-b-catenin and p27 respectively. Knockdown of PKM2 apparently decreased the level of PCNA, cyclinD1, p27 in primary astrocyte cells. Taken together, our findings indicate that nuclear translocation of PKM2 promotes astrocytes proliferation after SCI through modulating cell cycle signaling. These discoveries firstly uncovered the role of PKM2 in spinal cord injury and provided a potential therapeutic target for CNS injury and repair.

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Section: Discussionmentioning

confidence: 51%

Nuclear translocation of PKM2 modulates astrocyte proliferation via p27 and β-catenin pathway after spinal cord injury

et al. 2015

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“…One possible explanation is its capability of promoting the progression of human cancers [21]. For instance, PKM2 has been demonstrated to promote cell proliferation, migration, resistance to apoptosis, angiogenesis, autophagy, intratumoral inflammatory cell infiltration, and pre-metastatic niche formation in hepatocellular carcinomas.…”

Section: Discussionmentioning

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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“…Wen et. al claimed PKM2 as a hallmark of cancer whose expression levels were correlated with disease-free and overall survival in a cohort of 490 hepatocellular carcinoma patients 22 . Zhang et al .…”

Section: Discussionmentioning

confidence: 99%

High Expression of Pyruvate Kinase M2 is Associated with Chemosensitivity to Epirubicin and 5-Fluorouracil in Breast Cancer

Yuan

Liu

et al. 2015

J. Cancer

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Background: Pyruvate kinase M2 (PKM2) is the key enzyme in the Warburg effect, and it was recently reported to be involved in the metabolic pathways of chemotherapeutic drugs. However, the role of PKM2 in breast cancer and its influence in the sensitivity to front-line anticancer drugs remains unclear.Methods: In this study, we examined the correlation between the expression of PKM2 and the sensitivity of primary breast cancer cells to anticancer drugs. PKM2 expression was studied by immunohistochemistry using biopsy samples of 296 patients diagnosed with invasive breast carcinoma, and the collagen gel droplet embedded culture-drug sensitivity tests (CD-DST) was conducted to all the patients to detect in vitro chemosensitivity after surgery.Results: We found high PKM2 expression was significantly associated with in vitro chemosensitivity to epirubicin (EPI) (P=0.019) and 5-fluorouracil (5-Fu) (P=0.009) in breast cancer patients. Then we used a small group of neoadjuvant chemotherapy cases to confirm that the higher PKM2 expression, the better pathological response to therapy was obtained in patients treated with EPI-based or EPI plus 5-Fu chemotherapy regimens. Although univariate and multivariate analysis indicated that high PKM2 was a poor independent predictor of progression free survival (PFS) and overall survival (OS) in breast cancer, patients with PKM2 high expression who received EPI-based or EPI plus 5-Fu chemotherapy were found to have a longer PFS (P=0.003, P=0.013) and OS (P=0.003, P=0.004) than patients treated with non-EPI/5-Fu-based regimens, respectively.Conclusions: Our findings confirmed the poor prognosis of high PKM2 expression in breast cancer patients and revealed the predictive value of high PKM2 in the therapeutic response to EPI and 5-Fu. Moreover, our results provide the guidance of individual treatment for breast cancer patients who are foreboded a poor prognosis by the presence of high PKM2 status.

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

Cited by 37 publications

References 34 publications

Nuclear translocation of PKM2 modulates astrocyte proliferation via p27 and β-catenin pathway after spinal cord injury

Nuclear translocation of PKM2 modulates astrocyte proliferation via p27 and β-catenin pathway after spinal cord injury

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

High Expression of Pyruvate Kinase M2 is Associated with Chemosensitivity to Epirubicin and 5-Fluorouracil in Breast Cancer

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