Fructose and fructose kinase in cancer and other pathologies

Jiang, Hongfei; Lin, Qian; Ma, Leina; Luo, Shudi; Jiang, Xiaoming; Fang, Jing; Lu, Zhimin

doi:10.1016/j.jgg.2021.06.006

Cited by 19 publications

(17 citation statements)

References 89 publications

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“…It has been shown that multiple metabolic enzymes exert a noncanonical function in diverse cellular activities in tumor cells. Several metabolic enzymes, including phosphoglycerate kinase 1 (PGK1), pyruvate kinase M2 (PKM2), ketohexokinase isoform A (KHKA), phosphoenolpyruvate carboxykinase 1 (PCK1), and choline kinase α, can function as protein kinases and phosphorylate a variety of protein substrates to promote tumor development [27,28,33,36,[49][50][51][52][53][54][55][56][57][58][59][60]. Mitochondrial α-ketoglutarate dehydrogenase (α-KGDH) translocates into the nucleus and associates with KAT2A, which is known as a histone acetyltransferase.…”

Section: Discussionmentioning

confidence: 99%

A non‐metabolic function of hexokinase 2 in small cell lung cancer: promotes cancer cell stemness by increasing USP11‐mediated CD133 stability

Wang

Shao

Yang

et al. 2022

Cancer Communications

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Background Maintenance of cancer stem‐like cell (CSC) stemness supported by aberrantly regulated cancer cell metabolism is critical for CSC self‐renewal and tumor progression. As a key glycolytic enzyme, hexokinase 2 (HK2) plays an instrumental role in aerobic glycolysis and tumor progression. However, whether HK2 directly contribute to CSC stemness maintenance in small cell lung cancer (SCLC) is largely unclear. In this study, we aimed to investgate whether HK2 independent of its glycolytic activity is directly involved in stemness maintenance of CSC in SCLC. Methods Immunoblotting analyses were conducted to determine the expression of HK2 in SCLC CSCs and their differentiated counterparts. CSC‐like properties and tumorigenesis of SCLC cells with or without HK2 depletion or overexpression were examined by sphere formation assay and xenograft mouse model. Immunoprecipitation and mass spectrometry analyses were performed to identify the binding proteins of CD133. The expression levels of CD133‐associated and CSC‐relevant proteins were evaluated by immunoblotting, immunoprecipitation, immunofluorescence, and immunohistochemistry assay. RNA expression levels of Nanog, POU5F1, Lin28, HK2, Prominin‐1 were analyzed through quantitative reverse transcription PCR. Polyubiquitination of CD133 was examined by in vitro or in vivo ubiquitination assay. CD133+ cells were sorted by flow cytometry using an anti‐CD133 antibody. Results We demonstrated that HK2 expression was much higher in CSCs of SCLC than in their differentiated counterparts. HK2 depletion inhibited CSC stemness and promoted CSC differentiation. Mechanistically, non‐mitochondrial HK2 directly interacted with CD133 and enhanced CD133 expression without affecting CD133 mRNA levels. The interaction of HK2 and CD133 promoted the binding of the deubiquitinase ubiquitin‐specific protease 11 (USP11) to CD133, thereby inhibiting CD133 polyubiquitylation and degradation. HK2‐mediated upregulation of CD133 expression enhanced the expression of cell renewal regulators, SCLC cell stemness, and tumor growth in mice. In addition, HK2 expression was positively correlated with CD133 expression in human SCLC specimens, and their expression levels were associated with poor prognosis of SCLC patients. Conclusions These results revealed a critical non‐metabolic function of HK2 in promotion of cancer cell stemness. Our findings provided new insights into the multifaceted roles of HK2 in tumor development.

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Section: Discussionmentioning

confidence: 99%

A non‐metabolic function of hexokinase 2 in small cell lung cancer: promotes cancer cell stemness by increasing USP11‐mediated CD133 stability

Wang

Shao

Yang

et al. 2022

Cancer Communications

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“…Along with the rapid development of genomics and proteomics, glycomic analysis is gaining increasing attention in biological and biomedical studies of glycans. Glycans on cell surface or protein mediate numerous of critical biological functions, such as viral along and bacterial infection, inflammation, angiocardiopathy, embryogenesis and cancer ( Jiang et al, 2021a ; Tabang et al, 2021 ). On account of intricate structures as well as non-template-driven preparation, the glycans are usually hard to interrogate and manipulate compared with the other biomolecules, for instance, oligonucleotides and proteins.…”

Section: Glycan-based Tbc For In Vivo Imagingmentioning

confidence: 99%

Tetrazine bioorthogonal chemistry derived in vivo imaging

Zhao

Zhang

et al. 2022

Front. Mol. Biosci.

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Bioorthogonal chemistry represents plenty of highly efficient and biocompatible reactions that proceed selectively and rapidly in biological situations without unexpected side reactions towards miscellaneous endogenous functional groups. Arise from the strict demands of physiological reactions, bioorthogonal chemical reactions are natively selective transformations that are rarely found in biological environments. Bioorthogonal chemistry has long been applied to tracking and real-time imaging of biomolecules in their physiological environments. Thereinto, tetrazine bioorthogonal reactions are particularly important and have increasing applications in these fields owing to their unique properties of easily controlled fluorescence or radiation off-on mechanism, which greatly facilitate the tracking of real signals without been disturbed by background. In this mini review, tetrazine bioorthogonal chemistry for in vivo imaging applications will be attentively appraised to raise some guidelines for prior tetrazine bioorthogonal chemical studies.

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“…Currently, some important reviews have summarized the progress in the research on fructose metabolism (11,(17)(18)(19)(20)(21)(22)(23)(24). However, fructose consumption and its metabolic role in pig are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Fructose metabolism and its role in pig production: A mini-review

et al. 2022

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Epidemiological studies have shown that excessive intake of fructose is largely responsible for the increasing incidence of non-alcoholic fatty liver, obesity, and diabetes. However, depending on the amount of fructose consumption from diet, the metabolic role of fructose is controversial. Recently, there have been increasing studies reporting that diets low in fructose expand the surface area of the gut and increase nutrient absorption in mouse model, which is widely used in fructose-related studies. However, excessive fructose consumption spills over from the small intestine into the liver for steatosis and increases the risk of colon cancer. Therefore, suitable animal models may be needed to study fructose-induced metabolic changes. Along with its use in global meat production, pig is well-known as a biomedical model with an advantage over murine and other animal models as it has similar nutrition and metabolism to human in anatomical and physiological aspects. Here, we review the characteristics and metabolism of fructose and summarize observations of fructose in pig reproduction, growth, and development as well as acting as a human biomedical model. This review highlights fructose metabolism from the intestine to the blood cycle and presents the critical role of fructose in pig, which could provide new strategies for curbing human metabolic diseases and promoting pig production.

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Fructose and fructose kinase in cancer and other pathologies

Cited by 19 publications

References 89 publications

A non‐metabolic function of hexokinase 2 in small cell lung cancer: promotes cancer cell stemness by increasing USP11‐mediated CD133 stability

A non‐metabolic function of hexokinase 2 in small cell lung cancer: promotes cancer cell stemness by increasing USP11‐mediated CD133 stability

Tetrazine bioorthogonal chemistry derived in vivo imaging

Fructose metabolism and its role in pig production: A mini-review

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