The role of S-nitrosylation of PFKM in regulation of glycolysis in ovarian cancer cells

Gao, Wenwen; Huang, Mengqiu; Chen, Xi; Chen, Jianping; Zou, Zhiwei; Li, Linlin; Ji, Kaiyuan; Nie, Zhirui; Yang, Bo; Wei, Zibo; Xu, Pengfei; Jia, Jizeng; Zhang, Qianbing; Shen, Hong-Fen; Wang, Qianli; Li, Keyi; Zhu, Lei; Wang, Meng; Ye, Shuangyan; Zeng, Sisi; Lin, Ying; Rong, Zhili; Xu, Yang; Zhu, Peng; Zhang, Hui; Hao, Bingtao; Liu, Qiuzhen

doi:10.1038/s41419-021-03681-0

Cited by 24 publications

(13 citation statements)

References 42 publications

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“…NO-induced S-nitrosation activates oncogenic signaling cascades or directly alters activities of metabolic enzymes [ 26 ]. Our previous study showed that NOS1 expression in ovarian cancer promoted tumor glycolysis and growth through S-nitrasylation of the key enzyme (PFK1) [ 20 ]. In this study, we also observed that metabolic reprogramming is the major alteration in NOS1 deleted melanoma cells.…”

Section: Discussionmentioning

confidence: 99%

“…Unlike the other two isoforms, NOS1 interacts with target proteins through its unique PDZ domain, which ensures the effectiveness and selectivity of the NOS1 function [ 18 , 19 ]. Our study showed that NOS1 bound with the key enzyme of glycolysis and modulated metabolic rewiring in ovary cancer progression [ 20 ]. In melanoma, we found NOS1 expression correlated negatively with phosphorylation of STAT1 in IFN signal of patients PBMCs and predicted poor response to adoptive T cell therapy [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of NOS1 promotes the interferon response of melanoma cells

Liu

2022

J Transl Med

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Background NOS1 expression predicts poor prognosis in patients with melanoma. However, the molecular function of NOS1 in the type I IFN response and immune escape of melanoma is still unknown. Methods The CRISPR/Cas9 system was used to generate NOS1-knockout melanoma cells and the biological characteristics of NOS1-knockout cells were evaluated by MTT assay, clonogenic assay, EdU assay, and flow cytometric assay. The effect on tumor growth was tested in BALB/c-nu and C57BL/6 mouse models. The gene expression profiles were detected with Affymetrix microarray and RNA-seq and KEGG (Kyoto Encyclopedia of Genes and Genomes) and CLUE GO analysis was done. The clinical data and transcriptional profiles of melanoma patients from the public database TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus, GSE32611) were analyzed by Qlucore Omics Explorer. Results NOS1 deletion suppressed the proliferation of melanoma A375 cells in culture, blocked cell cycling at the G0/G1 phase, and decreased the tumor growth in lung metastasis nodes in a B16 melanoma xenograft mouse model. Moreover, NOS1 knockout increased the infiltration of CD3+ immune cells in tumors. The transcriptomics analysis identified 2203 differential expression genes (DEGs) after NOS1 deletion. These DEGs indicated that NOS1 deletion downregulated mostly metabolic functions but upregulated immune response pathways. After inhibiting with NOS1 inhibitor N-PLA, melanoma cells significantly increased the response to IFN$$\upalpha $$ α by upregulation expression of IFN$$\upalpha $$ α simulation genes (ISGs), especially the components in innate immune signaling, JAK-STAT, and TOLL-LIKE pathway. Furthermore, these NOS1-regulating immune genes (NOS1-ISGs) worked as a signature to predict poor overall survival and lower response to chemotherapy in melanoma patients. Conclusion These findings provided a transcriptional evidence of NOS1 promotion on tumor growth, which is correlated with metabolic regulation and immune escape in melanoma cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibition of NOS1 promotes the interferon response of melanoma cells

Liu

2022

J Transl Med

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“…A key glycolytic regulatory enzyme, PFKM, which is concerned as an energy activator of muscle glycolysis, is encoded by the PFKM gene. Recently, there have been several researches focused on the association between PFKM mutations and different types of cancers, such as bladder cancer (22), breast cancer (23), and ovarian cancer (24), etc. The funny fact that most of these cancers are also highly correlated with hormones (25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

Association of PFKM gene polymorphisms and susceptibility to cryptorchidism in a Chinese Han population

et al. 2022

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Cryptorchidism is one of the most common congenital anomalies in newborn boys. There are various risk factors that have been veri ed to have relationship with cryptorchidism, including exogenous and genetic, but the pathogenesis of cryptorchidism remains unclear. PFKM gene is a critical gene encodes for a regulatory enzyme, which limits the rate in the pathway of glycolysis. In order to investigate the possible association between PFKM gene polymorphisms and cryptorchidism risk, 3 tag SNPs of PFKM gene, rs2228500 (A/G), rs4075913(A/G), and rs11168417(C/T) were selected and genotyped in a hospitalbased case-control study involving 140 cryptorchidism patients and 227 healthy controls. The frequency of allele G of SNP rs2228500 is increased in cryptorchidism patients compared to that in controls (p < 0.05). Genotypic frequencies of rs2228500 are associated with the susceptibility of cryptorchidism in the codominant model (p < 0.05). And compared with G/G genotype in the dominant model, notable decreased frequencies of A carriers (A/G-A/A genotypes) were observed in cryptorchidism patients (p = 0.0069, OR = 1.80, 95% CI =1.17-2.75). This research rstly revealed that PFKM gene polymorphisms were associated with cryptorchidism in a Chinese Han population.

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“…This suggests that Nur77 may be a potential target for the treatment of melanoma 1422 . In the glycolysis pathway, PFKM is one of the most important regulatory enzymes, and SNO at C351 of PFKM can stabilize the tetramer of PFKM, which contributes to the metabolic reprogramming of ovarian cancer cells 1423 . Additionally, elevated expression of Nm23‐H1 is linked to a favorable prognosis in patients with breast cancer, and activation of Nm23‐H1 through redox regulation can inhibit breast cancer metastasis 1424 .…”

Section: Redox Modificationsmentioning

confidence: 99%

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Zhong

Xiao

Xie

et al. 2023

MedComm

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Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on the backbones or amino acid side chains of proteins and expand the diversity of proteins, which provides the basis for the emergence of organismal complexity. To date, more than 650 types of protein modifications, such as the most well‐known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short‐chain and long‐chain acylation modifications, redox modifications, and irreversible modifications, have been described, and the inventory is still increasing. By changing the protein conformation, localization, activity, stability, charges, and interactions with other biomolecules, PTMs ultimately alter the phenotypes and biological processes of cells. The homeostasis of protein modifications is important to human health. Abnormal PTMs may cause changes in protein properties and loss of protein functions, which are closely related to the occurrence and development of various diseases. In this review, we systematically introduce the characteristics, regulatory mechanisms, and functions of various PTMs in health and diseases. In addition, the therapeutic prospects in various diseases by targeting PTMs and associated regulatory enzymes are also summarized. This work will deepen the understanding of protein modifications in health and diseases and promote the discovery of diagnostic and prognostic markers and drug targets for diseases.

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The role of S-nitrosylation of PFKM in regulation of glycolysis in ovarian cancer cells

Cited by 24 publications

References 42 publications

Inhibition of NOS1 promotes the interferon response of melanoma cells

Inhibition of NOS1 promotes the interferon response of melanoma cells

Association of PFKM gene polymorphisms and susceptibility to cryptorchidism in a Chinese Han population

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

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