Acetylation of PGK1 promotes liver cancer cell proliferation and tumorigenesis

Hu, Hongli; Zhu, Wenwei; Qin, Jun; Chen, Min; Gong, Liyan; Li, Long; Lei, Yu; Tao, Yongzhen; Yin, Huiyong; Zhou, Hu; Zhou, Lisha; Ye, Dan; Ye, Qing–Hai; Gao, Daming

doi:10.1002/hep.28887

Cited by 204 publications

(190 citation statements)

References 45 publications

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“…PGK1, an important enzyme in metabolic glycolysis, has been considered as an oncogene in various human malignancies . PGK1 is upregulated in HCC and negatively correlated to poor survival in patients with HCC . Consistently, we also observed significant overexpression of PGK1 mRNA and protein in HCC specimens.…”

Section: Discussionsupporting

confidence: 86%

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MicroRNA‐450b‐3p inhibits cell growth by targeting phosphoglycerate kinase 1 in hepatocellular carcinoma

Chen

Zhuang

Wang

et al. 2019

J of Cellular Biochemistry

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Dysregulation of microRNAs frequently contributes to the occurrence and progression of human diseases, including hepatocellular carcinoma (HCC). In this study, the role of miR‐450b‐3p in HCC was investigated. Gene Expression Omnibus database and HCC specimens were used to evaluate the expression level of miR‐450b‐3p and the patient's prognosis. Cell functional analyses and tumor xenograft model were used to assess the role of miR‐450b‐3p in HCC. Bioinformatics was used to predict the downstream target gene of miR‐450b‐3p, which was verified by dual‐luciferase reporter assay. MiR‐450b‐3p was found to be downregulated in HCC cell lines and tissues, compared with nontransformed immortal hepatic cells and adjacent normal liver tissues, respectively. Lower expression of miR‐450b‐3p was associated with poor overall survival and disease‐free survival in patients with HCC. Ectopic expression of miR‐450b‐3p inhibited HCC cell viability, colony formation, and cell‐cycle progression in vitro, and suppressed the growth of HCC xenograft tumors in vivo. Interestingly, a negative correlation between miR‐450b‐3p and phosphoglycerate kinase 1 (PGK1) protein was observed among HCC specimens. Additionally, miR‐450b‐3p inhibited PGK1 expression and phosphorylation of protein kinase B in HCC cell lines. Further experiments confirmed that PGK1 was a direct target of miR‐450b‐3p. Moreover, restoration of PGK1 abrogated the inhibitory effect of miR‐450b‐3p on HCC proliferation and cell division. In conclusion, miR‐450b‐3p is downregulated in human HCC and exerts tumor suppressive effects at least in part by inhibiting PGK1.

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Section: Discussionsupporting

confidence: 86%

“…These results indicated that PGK1 is a direct target of miR‐450b‐3p in HCC. Notably, the inhibitory effect of miR‐450b‐3p on HCC proliferation could be abrogated by overexpression of PGK1 which has been reported to promote the tumorigenesis and development of HCC …”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐450b‐3p inhibits cell growth by targeting phosphoglycerate kinase 1 in hepatocellular carcinoma

Chen

Zhuang

Wang

et al. 2019

J of Cellular Biochemistry

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“…In our surgical samples we have identified three distinct isoforms of PGK1 all increased with respect to the normal tissues. Many types of cancers, including those of the breast [47], the colon [48], the liver [49] and others, have been shown to exhibit an increased expression of PGK1. Indeed, it has been demonstrated that, in addition to its role as a glycolytic enzyme, PGK1 may act as a promoter of cancer progression and induce chemoresistance for some type of drugs [47,48].…”

Section: Phosphoglycerate Kinase 1 Pgk1 (Pgk1)mentioning

confidence: 99%

Retrospective Proteomic Screening of 100 Breast Cancer Tissues

Pucci‐Minafra¹,

Cara²,

Musso³

et al. 2017

Preprint

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Abstract:The present investigation has been conducted on one hundred tissue fragments of breast cancer, collected and immediately cryopreserved following the surgical resection. The fragments were selected from patients with invasive ductal carcinoma of the breast, the most common and potentially aggressive type of mammary cancer, with the objective to increase the knowledge of breast cancer molecular markers, useful for diagnostic and prognostic categorization of patients, in assessing postsurgical therapeutic regimes. The proteomic screening, by 2D-IPG and mass spectrometry, allowed us to identify two main classes of protein clusters: proteins expressed ubiquitously at high levels in all patients, and proteins expressed sporadically among the same patients. Within the group of ubiquitous proteins, glycolytic enzymes and proteins with anti-apoptotic activity were predominant. Among the sporadic ones, proteins involved in cell motility, molecular chaperones and proteins involved in the detoxification appeared prevalent. The data of the present study indicates that the primary tumor growth is generally supported by two concurrent pathways: the inhibition of apoptosis and the stimulation of cellular proliferation. The second phase of the evolution of the tumor can be prematurely scheduled by the occasional presence of proteins involved in cell motility and in the defenses of the oxidative stress. To our knowledge this report on large-scales proteomics of breast cancer is currently a unique approach in the literature that offers the opportunity to evaluate the presence and recurrence of proteins to be used as prognostic indicators and susceptibility to metastasis in patients operated on for invasive ductal carcinoma of the breast.

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“…Cancer cells exhibit a series of common features, including uncontrolled proliferation, resistance to programmed cell death, and enhanced metastasis ability [1,2]. Of these, alteration of metabolic pathways is regarded as a driving force of tumor initiation and progression [2,3].…”

Section: Introductionmentioning

confidence: 99%

“…PGK1 and pyruvate kinase M2 (PKM2) are the only enzymes that control production of ATP during aerobic glycolysis in cancer cells [1,3]. In addition to the important role of PGK1 in glycolysis, there are reports of its role in cancer.…”

Section: Introductionmentioning

confidence: 99%

PGK1 is a Potential Survival Biomarker and Invasion Promoter by Regulating the HIF-1α–Mediated Epithelial-Mesenchymal Transition Process in Breast Cancer

Wei

et al. 2018

Cell Physiol Biochem

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Background/Aims: Glycolysis, a multi-step enzymatic reaction, is considered to be the root of cancer development and progression. The aim of this study is to figure out which glycolysis enzyme participates in the progression of breast cancer and its possible mechanisms. Materials: We firstly screened out PGK1 by performing an RT-PCR array of glycolysis-related genes in three paired breast cancer samples, and further investigated PGK1 using TCGA and our own database. The effect and mechanism of PGK1 on cell invasion was further explored both in vitro and using patient samples. Results: PGK1 was most upregulated in T3N0 with distant metastases compared to those with no metastases. In the TCGA database, high PGK1 expression predicted poor overall survival (OS) in breast cancer and some other cancers (P< 0.001). In the validation cohort, high PGK1 expression was significantly correlated with larger tumor size (P=0.011) and advanced TNM stage (P=0.033), and PGK1 expression was an independent prognostic factor for OS and disease free survival (DFS) in both univariate and multivariate regression analyses (P< 0.05). Functional studies indicated that knockdown of PGK1 expression significantly inhibited invasion and reversed the epithelial-mesenchymal transition process in breast cancer cells (P< 0.05). Mechanistically, PGK1 increased HRE luciferase activity in a dose-dependent manner, while silencing PGK1 expression decreased HRE activity. Conclusion: High PGK1 expression was associated with poor prognosis in breast cancer, because PGK1 and HIF-1α formed a positive feed-forward loop and thus stimulated breast cancer progression and metastases. Based on these results, PGK1 may serve as a promising biomarker and target therapy for breast cancer.

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Acetylation of PGK1 promotes liver cancer cell proliferation and tumorigenesis

Abstract: These findings demonstrate a novel regulation of PGK1 as well as its important role in liver cancer progression. (Hepatology 2017;65:515-528).

Cited by 204 publications

References 45 publications

MicroRNA‐450b‐3p inhibits cell growth by targeting phosphoglycerate kinase 1 in hepatocellular carcinoma

MicroRNA‐450b‐3p inhibits cell growth by targeting phosphoglycerate kinase 1 in hepatocellular carcinoma

Retrospective Proteomic Screening of 100 Breast Cancer Tissues

PGK1 is a Potential Survival Biomarker and Invasion Promoter by Regulating the HIF-1α–Mediated Epithelial-Mesenchymal Transition Process in Breast Cancer

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