Enolase 1, a Moonlighting Protein, as a Potential Target for Cancer Treatment

Qiao, Gan; Wu, Anguo; Chen, Xiaoliang; Tian, Ye; Lin, Xiukun

doi:10.7150/ijbs.63556

Cited by 69 publications

(44 citation statements)

References 109 publications

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“…The other genes with higher RNA expression in Cluster 2 were ISG20 and CLIC3; both are implicated in tumor progression (Alsheikh et al, 2021; Hernandez‐Fernaud et al, 2017), suggesting they may contribute to the greater fold expansion we observed in the conditions containing 41BBL (Figure 2a). On the other hand, ENO1, which is a key glycolysis enzyme with pleiotropic roles in growth and differentiation (Qiao et al, 2021), was increased in RNA levels in clusters (3 and 5) that were mostly resulted from cells cultured with K562 alone or K562 expressing mIL15, suggesting a role in the phenotypic differences of the cytokine‐induced NK cells.…”

Section: Resultsmentioning

confidence: 99%

Differential effects on natural killer cell production by membrane‐bound cytokine stimulations

Chang

Tang

Nelson

et al. 2022

Biotech & Bioengineering

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Robust manufacturing production of natural killer (NK) cells has been challenging in allogeneic NK cell-based therapy. Here, we compared the impact of cytokines on NK cell expansion by developing recombinant K562 feeder cell lines expressing membrane-bound cytokines, mIL15, mIL21, and 41BBL, individually or in combination. We found that 41BBL played a dominant role in promoting up to 500,000-fold of NK cell expansion after a 21-day culture process without inducing exhaustion.However, 41BBL stimulation reduced the overall cytotoxic activity of NK cells when combined with mIL15 and/or mIL21. Additionally, long-term stimulation with mIL15 and/or mIL21, but not 41BBL, increased CD56 expression and the CD56 bright population, which is unexpectedly correlated with NK cell cytotoxicity. By conducting single-cell sequencing, we identified distinct subpopulations of NK cells induced by different cytokines, including an adaptive-like CD56 bright CD16 -CD49a + subset induced by mIL15. Through gene expression analysis, we found that different cytokines modulated signaling pathways and target genes involved in cell cycle, senescence, self-renewal, migration, and maturation in different ways. Together, our study demonstrates that cytokine signaling pathways play distinct roles in NK cell

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Section: Resultsmentioning

confidence: 99%

Differential effects on natural killer cell production by membrane‐bound cytokine stimulations

Chang

Tang

Nelson

et al. 2022

Biotech & Bioengineering

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“…A more direct role of enolase and aldolase is suggested by studies that show these two enzymes have roles well beyond their well-known function in glycolysis. Enolase-1 has been shown to localize to the plasma membrane as a plasminogen receptor as well as function as a DNA binding protein in the process of transcription and has involvement in multiple signal transduction pathways [ 75 ]. Aldolase A has already been implicated as an actin-binding protein that regulates polymerization of actin [ 76 ].…”

Section: Discussionmentioning

confidence: 99%

Protein interactions with metallothionein-3 promote vectorial active transport in human proximal tubular cells

et al. 2022

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Metallothionein 3 (MT-3) is a small, cysteine-rich protein that binds to essential metals required for homeostasis, as well as to heavy metals that have the potential to exert toxic effects on cells. MT-3 is expressed by epithelial cells of the human kidney, including the cells of the proximal tubule. Our laboratory has previously shown that mortal cultures of human proximal tubular (HPT) cells express MT-3 and form domes in the cell monolayer, a morphological feature indicative of vectorial active transport, an essential function of the proximal tubule. However, an immortalized proximal tubular cell line HK-2 lacks the expression of MT-3 and fails to form domes in the monolayer. Transfection of HK-2 cells with the MT-3 gene restores dome formation in these cells suggesting that MT-3 is required for vectorial active transport. In order to determine how MT-3 imparts this essential feature to the proximal tubule, we sought to identify proteins that interact either directly or indirectly with MT-3. Using a combination of pulldowns, co-immunoprecipitations, and mass spectrometry analysis, putative protein interactants were identified and subsequently confirmed by Western analysis and confocal microscopy, following which proteins with direct physical interactions were investigated through molecular docking. Our data shows that MT-3 interacts with myosin-9, aldolase A, enolase 1, β-actin, and tropomyosin 3 and that these interactions are maximized at the periphery of the apical membrane of doming proximal tubule cells. Together these observations reveal that MT-3 interacts with proteins involved in cytoskeletal organization and energy metabolism, and these interactions at the apical membrane support vectorial active transport and cell differentiation in proximal tubule cultures.

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“…ENO1 is a multifunctional protein which implicated in critical biological progression pathways in cancers. As a glycolytic enzyme, ENO1 contributes to the Warburg effect and provides ATP to promote cancer development and progression [45]. In addition, ENO1 promotes the plasminogen activation system and upregulates integrin to enhance the migration and invasion of cancers [46][47][48]; ENO1 regulates gastric cancer cells stemness by stimulating glycolysis [49].…”

Section: Discussionmentioning

confidence: 99%

CCDC65, a Gene Knockout that leads to Early Death of Mice, acts as a potentially Novel Tumor Suppressor in Lung Adenocarcinoma

Zhang¹,

Xu²,

Hu³

et al. 2022

Int. J. Biol. Sci.

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CCDC65 is a member of the coiled-coil domain-containing protein family and was only reported in gastric cancer by our group. We first observed that it is downregulated in lung adenocarcinoma based on the TCGA database. Reduced CCDC65 protein was shown as an unfavorable factor promoting the clinical progression in lung adenocarcinoma. Subsequently, CCDC65 -/-mice were found possibly dead of hydrocephalus. Compared with the CCDC65 +/+ mice, the downregulation of CCDC65 in CCDC65 +/mice significantly increased the formation ability of lung cancer induced by urethane. In the subsequent investigation, we observed that CCDC65 functions as a tumor suppressor repressing cell proliferation in vitro and in vivo. Molecular mechanism showed that CCDC65 recruited E3 ubiquitin ligase FBXW7 to induce the ubiquitination degradation of c-Myc, an oncogenic transcription factor in tumors, and reduced c-Myc binding to ENO1 promoter, which suppressed the transcription of ENO1. In addition, CCDC65 also recruited FBXW7 to degrade ENO1 protein by ubiquitinated modulation. The downregulated ENO1 further reduced the phosphorylation activation of AKT1, which thus inactivated the cell cycle signal. Our data demonstrated that CCDC65 is a potential tumor suppressor by recruiting FBWX7 to suppress c-Myc/ENO1-induced cell cycle signal in lung adenocarcinoma.

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Enolase 1, a Moonlighting Protein, as a Potential Target for Cancer Treatment

Cited by 69 publications

References 109 publications

Differential effects on natural killer cell production by membrane‐bound cytokine stimulations

Differential effects on natural killer cell production by membrane‐bound cytokine stimulations

Protein interactions with metallothionein-3 promote vectorial active transport in human proximal tubular cells

CCDC65, a Gene Knockout that leads to Early Death of Mice, acts as a potentially Novel Tumor Suppressor in Lung Adenocarcinoma

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