Pyruvate kinase M2 (PKM2) in cancer and cancer therapeutics

Zhu, Susi; Guo, Yeye; Zhang, Xu; Liu, Hong; Yin, Mingzhu; Chen, Xiang; Peng, Cong

doi:10.1016/j.canlet.2020.11.018

Cited by 134 publications

(85 citation statements)

References 105 publications

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“…LncRNAs may enhance the expression of glycolytic key enzymes to promote glycolytic level and progression in cancer cells. They interacted with transcription factor receptors, such as aryl hydrocarbon receptor, then promoted the transcriptional expression of glycolytic key enzymes, such as hexokinase 2 or pyruvate kinase M2, facilitated cancer cells progression ( 18 , 19 ). LncRNA inhibited enzymes degradation by reducing the modification of key enzymes, such as ubiquitination ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of a Three-Glycolysis-Related lncRNA Signature Correlated With Prognosis and Metastasis in Clear Cell Renal Cell Carcinoma

Tong

Zhu

et al. 2022

Front. Med.

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The clear cell renal cell carcinoma (ccRCC) is not only a malignant disease but also an energy metabolic disease, we aimed to identify a novel prognostic model based on glycolysis-related long non-coding RNA (lncRNAs) and explore its mechanisms. With the use of Pearson correlation analysis between the glycolysis-related differentially expressed genes and lncRNAs from The Cancer Genome Atlas (TCGA) dataset, we identified three glycolysis-related lncRNAs and successfully constructed a prognostic model based on their expression. The diagnostic efficacy and the clinically predictive capacity of the signature were evaluated by univariate and multivariate Cox analyses, Kaplan–Meier survival analysis, and principal component analysis (PCA). The glycolysis-related lncRNA signature was constructed based on the expressions of AC009084.1, AC156455.1, and LINC00342. Patients were grouped into high- or low-risk groups according to risk score demonstrated significant differences in overall survival (OS) period, which were validated by patients with ccRCC from the International Cancer Genome Consortium (ICGC) database. Univariate Cox analyses, multivariate Cox analyses, and constructed nomogram-confirmed risk score based on our signature were independent prognosis predictors. The CIBERSORT algorithms demonstrated significant correlations between three-glycolysis-related lncRNAs and the tumor microenvironment (TME) components. Functional enrichment analysis demonstrated potential pathways and processes correlated with the risk model. Clinical samples validated expression levels of three-glycolysis-related lncRNAs, and LINC00342 demonstrated the most significant aberrant expression. in vitro, the general overexpression of LINC00342 was detected in ccRCC cells. After silencing LINC00342, the aberrant glycolytic levels and migration abilities in 786-O cells were decreased significantly, which might be explained by suppressed Wnt/β-catenin signaling pathway and reversed Epithelial mesenchymal transformation (EMT) process. Collectively, our research identified a novel three-glycolysis-related lncRNA signature as a promising model for generating accurate prognoses for patients with ccRCC, and silencing lncRNA LINC00342 from the signature could partly inhibit the glycolysis level and migration of ccRCC cells.

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Section: Discussionmentioning

confidence: 99%

Identification of a Three-Glycolysis-Related lncRNA Signature Correlated With Prognosis and Metastasis in Clear Cell Renal Cell Carcinoma

Tong

Zhu

et al. 2022

Front. Med.

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“…In addition, the expression of GLUT1, which is an important glucose transporter [ 24 ], was decreased after Rh2 treatment. PKM2, one of the key enzymes in the glycolysis process, is involved in the production of pyruvate [ 25 ]. LDHA functions as a key enzyme in the last step of the glycolysis pathway and catalyzes the conversion of pyruvate to lactate [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rh2 Inhibits Glycolysis through the STAT3/c-MYC Axis in Non-Small-Cell Lung Cancer

Sun

Zhao

et al. 2021

Journal of Oncology

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Ginsenoside Rh2 (Rh2) is one of the pharmacologically active components of ginseng with an antitumor effect. However, its effect on non-small-cell lung cancer (NSCLC), especially on aerobic glycolysis, which plays a crucial role in the proliferation and progression of tumor cells, has not been characterized. Here, we demonstrated that Rh2 inhibited the proliferation and metastasis of NSCLC cells by promoting apoptosis and suppressing epithelial-mesenchymal transition, respectively. Notably, Rh2 exerted a glycolysis inhibition effect through regulating GLUT1, PKM2, and LDHA, which are key enzymes of the glycolysis process. Furthermore, the metabolic shift function of Rh2 was dependent on the STAT3/c-Myc axis in NSCLC. This novel regulatory role of Rh2 provides a new perspective for NSCLC treatment and highlights the potentiality of Rh2 to be used as a tumor energy blocker. The combination of Rh2 with an STAT3 or c-Myc inhibitor revealed a promising therapeutic approach for patients with NSCLC.

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“…PKM2, a key glycolysis enzyme, is overexpressed in many tumor cells and plays a critical role as a regulator in tumor metabolism [ 169 ]. PKM2 has been demonstrated to be overexpressed in PC and promotes PC metastasis via ERK-cyclooxygenase (COX-2) [ 170 ].…”

Section: Pks and Pc Progressionmentioning

confidence: 99%

Targeting Protein Kinases and Epigenetic Control as Combinatorial Therapy Options for Advanced Prostate Cancer Treatment

et al. 2022

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Prostate cancer (PC), the fifth leading cause of cancer-related mortality worldwide, is known as metastatic bone cancer when it spreads to the bone. Although there is still no effective treatment for advanced/metastatic PC, awareness of the molecular events that contribute to PC progression has opened up opportunities and raised hopes for the development of new treatment strategies. Androgen deprivation and androgen-receptor-targeting therapies are two gold standard treatments for metastatic PC. However, acquired resistance to these treatments is a crucial challenge. Due to the role of protein kinases (PKs) in the growth, proliferation, and metastases of prostatic tumors, combinatorial therapy by PK inhibitors may help pave the way for metastatic PC treatment. Additionally, PC is known to have epigenetic involvement. Thus, understanding epigenetic pathways can help adopt another combinatorial treatment strategy. In this study, we reviewed the PKs that promote PC to advanced stages. We also summarized some PK inhibitors that may be used to treat advanced PC and we discussed the importance of epigenetic control in this cancer. We hope the information presented in this article will contribute to finding an effective treatment for the management of advanced PC.

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Pyruvate kinase M2 (PKM2) in cancer and cancer therapeutics

Cited by 134 publications

References 105 publications

Identification of a Three-Glycolysis-Related lncRNA Signature Correlated With Prognosis and Metastasis in Clear Cell Renal Cell Carcinoma

Identification of a Three-Glycolysis-Related lncRNA Signature Correlated With Prognosis and Metastasis in Clear Cell Renal Cell Carcinoma

Ginsenoside Rh2 Inhibits Glycolysis through the STAT3/c-MYC Axis in Non-Small-Cell Lung Cancer

Targeting Protein Kinases and Epigenetic Control as Combinatorial Therapy Options for Advanced Prostate Cancer Treatment

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