Protein kinase function of pyruvate kinase M2 and cancer

Chen, Xun; Chen, Shangwu; Yu, Dongsheng

doi:10.1186/s12935-020-01612-1

Cited by 54 publications

(50 citation statements)

References 106 publications

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“…7C,D ). Transcription of several genes, including cyclin D, GLUT1, HK1, LDHA, MEK5, MYC, PDK1, and VEGFA, has been reported to be enhanced by PKM2 in the nucleus via its transcriptional co‐activating functions [ 25 , 26 ]. We further explored whether increased level of nuclear PKM2 induced by PSMD14 participates in transcriptional regulation of these genes.…”

Section: Resultsmentioning

confidence: 99%

Deubiquitinase PSMD14 promotes ovarian cancer progression by decreasing enzymatic activity of PKM2

Sun

Liu

et al. 2021

Molecular Oncology

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Dysregulation of deubiquitination has been reported to contribute to carcinogenesis. However, the function and mechanism of deubiquitinating enzyme 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) in the progression of ovarian cancer (OV), the deadliest gynecological cancer, still remains to be characterized. The present study demonstrated that PSMD14 was overexpressed in OV tissues and its higher levels correlated with a higher International Federation of Gynecology and Obstetrics (FIGO) stage in OV patients. A high level of PSMD14 expression was related to poor survival in OV patients. Knockdown and overexpression experiments elucidated that PSMD14 stimulated OV cell proliferation, invasion, and migration in vitro. Repression of PSMD14 suppressed OV tumor growth in vivo. PSMD14 inhibitor O-phenanthroline (OPA) effectively attenuated malignant behaviors of OV cells in vitro and OV tumor growth in vivo. Mechanistically, we uncovered that PSMD14 was involved in post-translational regulation of pyruvate kinase M2 isoform (PKM2). PSMD14 decreased K63-linked ubiquitination on PKM2, downregulated the ratio of PKM2 tetramers to dimers and monomers, and subsequently diminished pyruvate kinase activity and induced nuclear translocation of PKM2, contributing to aerobic glycolysis in OV cells. Collectively, our findings highlight the potential roles of PSMD14 as a biomarker and therapeutic candidate for OV.

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Section: Resultsmentioning

confidence: 99%

Deubiquitinase PSMD14 promotes ovarian cancer progression by decreasing enzymatic activity of PKM2

Sun

Liu

et al. 2021

Molecular Oncology

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“… 39 Tumor cells usually express PKM2, which plays an important role in cancer growth and carbohydrate metabolism. 40 The dimeric form of PKM2 (restrictive) promotes the anabolism of intermediate biological macromolecules of glucose, while the tetrameric structure (activated) promotes the OXPHOS of glucose and provides energy for cells. 41 The overexpression of PKM2 and the transformation between dimers and tetramers of PKM2 enable tumor cells to survive in various oxygen as well as nutrient environments.…”

Section: Circrnas In Regulating Enzymes or Kinases Of Glycolysismentioning

confidence: 99%

“…39 Tumor cells usually express PKM2, which plays an important role in cancer growth and carbohydrate metabolism. 40 The dimeric form of PKM2 (restrictive) promotes the anabolism of intermediate biological macromolecules of glucose, while the tetrameric structure Figure 3 Mechanism of circRNA binding to microRNA. On the left, it shows the regulatory effects of microRNA on tumor glucose metabolism under normal conditions, and the ago-microRNA complexes can bind to transporters, enzymes, transcription factors or genes, signaling pathways and produce regulatory effects.…”

Section: Pkm2mentioning

confidence: 99%

Tip of the Iceberg: Roles of CircRNAs in Cancer Glycolysis

Tan¹,

Xian²,

Dai³

et al. 2021

OTT

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Warburg effect reflects that tumor cells tend to generate energy by aerobic glycolysis rather than oxidative phosphorylation (OXPHOS), thus promoting the development of malignant tumors. As a kind of non-coding RNA, circular RNA (circRNA) is characterized by a closed ring structure and emerges as a regulator of cancer metabolism. Mounting studies revealed that circRNA can regulate the cancer metabolism process through affecting the expression of glycolysis relevant enzymes, transcription factors (TFs), and signaling pathways. In this review, we comprehensively analyzed and concluded the mechanism of circRNA regulating glycolysis, hoping to deepen the cognition of the cancer metabolic regulatory network and to reap huge fruits in targeted cancer treatment.

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“…The final rate-limiting step of glycolysis is pyruvate kinase (PKM1) [15,35] . While PKM1 is expressed in most tissues and serves only to phosphorylate PEP, PKM2 is frequently overexpressed in cancers and acts as a strict checkpoint to regulate the metabolic demands of cancer cells [41,42] . PKM2 is often found as a tetramer, in which it forms pyruvate from PEP.…”

Section: Pyruvate Kinasementioning

confidence: 99%

Review of pharmacological inhibition of thyroid cancer metabolism

Davidson¹,

Carr²

2021

JCMT

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Thyroid cancer (TC) is the most common malignancy of the endocrine system and has been rapidly increasing in incidence over the past few decades. Aggressive TCs metastasize quickly and often levy poor prognoses, as they are frequently resistant to first-line treatment options. Patients diagnosed with aggressive, dedifferentiated TC have a prognosis of under a year with the most current treatment modalities. Like many cancers, TCs also exhibit altered cell metabolism, which enhances the cell's ability to generate energy, protect against reactive oxygen species, and synthesize macromolecules such as lipids, proteins, and nucleotides for proliferation. Genetic and enzyme profiling of TC tissues and cell lines have uncovered several dysregulated metabolic pathways such as glycolysis, the pentose phosphate pathway, glutamine metabolism, and pyrimidine synthesis. These aberrations are most often due to overexpression of rate-limiting enzymes or metabolite transporters. Metabolic pathways pose attractive therapeutic targets in aggressive TC and may serve to work in tandem with standard therapeutics such as kinase inhibitors depending on the genetic, metabolic, and signaling backgrounds of individual tumors. Further studies are needed to clearly delineate altered metabolic targets across TC subtypes for implementing therapeutic metabolic inhibitors that have shown success in other aggressive tumors.

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Protein kinase function of pyruvate kinase M2 and cancer

Cited by 54 publications

References 106 publications

Deubiquitinase PSMD14 promotes ovarian cancer progression by decreasing enzymatic activity of PKM2

Deubiquitinase PSMD14 promotes ovarian cancer progression by decreasing enzymatic activity of PKM2

Tip of the Iceberg: Roles of CircRNAs in Cancer Glycolysis

Review of pharmacological inhibition of thyroid cancer metabolism

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