A pan-cancer analysis of the role of hexokinase II (HK2) in human tumors

Li, Ruiqi; Mei, Shuchong; Ding, Qiang; Wang, Qing-Ming; Yu, Li; Zi, Fuming

doi:10.1038/s41598-022-23598-8

Cited by 11 publications

(9 citation statements)

References 42 publications

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“…This in-silico approach should explain, at least in part, the in-vitro assays, which were based on the quantification of cell viability. For this reason, some of the molecular targets highly expressed in a variety of cancer cells and related to this process are those belonging to the Bcl-2 family (Mcl-1 and Bcl-xL) [ 46 ], anti-apoptotic proteins, and hexokinase 2 (HK2), which plays a central role in the cellular uptake and utilization of glucose [ 47 ]. The anti-apoptotic Bcl-2 proteins protect against cell death by apoptosis and also allow senescent cells to survive [ 48 ], and it has been suggested that they might appear in the early phase of carcinogenesis in the stomach [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic Activity of Amaryllidaceae Plants against Cancer Cells: Biotechnological, In Vitro, and In Silico Approaches

et al. 2023

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Cancer is a major cause of death and an impediment to increasing life expectancy worldwide. With the aim of finding new molecules for chemotherapeutic treatment of epidemiological relevance, ten alkaloid fractions from Amaryllidaceae species were tested against six cancer cell lines (AGS, BT-549, HEC-1B, MCF-7, MDA-MB 231, and PC3) with HaCat as a control cell line. Some species determined as critically endangered with minimal availability were propagated using in vitro plant tissue culture techniques. Molecular docking studies were carried out to illustrate binding orientations of the 30 Amaryllidaceae alkaloids identified in the active site of some molecular targets involved with anti-cancer activity for potential anti-cancer drugs. In gastric cancer cell line AGS, the best results (lower cell viability percentages) were obtained for Crinum jagus (48.06 ± 3.35%) and Eucharis bonplandii (45.79 ± 3.05%) at 30 µg/mL. The research focused on evaluating the identified alkaloids on the Bcl-2 protein family (Mcl-1 and Bcl-xL) and HK2, where the in vitro, in silico and statistical results suggest that powelline and buphanidrine alkaloids could present cytotoxic activity. Finally, combining experimental and theoretical assays allowed us to identify and characterize potentially useful alkaloids for cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Cytotoxic Activity of Amaryllidaceae Plants against Cancer Cells: Biotechnological, In Vitro, and In Silico Approaches

et al. 2023

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“…Our analysis of Kaplan–Meier plots derived from data on 1925 lung cancer patients clearly confirmed the strong oncogenic role of HK2, LDHA, PHGDH, PSAT1, SHMT2, MTHFD2, c-Myc, and ATF4 (CREB-2) in lung cancer. The high expression of genes coding for all of these enzymes and their transcriptional regulators is strongly associated with a shortened patient survival in different types of malignancies [ 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ].…”

Section: Discussionmentioning

confidence: 99%

20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells

Shuvalov,

Kirdeeva,

Fefilova

et al. 2023

Metabolites

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20-Hydroxyecdysone (20E) is an arthropod hormone which is synthesized by some plants as part of their defense mechanism. In humans, 20E has no hormonal activity but possesses a number of beneficial pharmacological properties including anabolic, adaptogenic, hypoglycemic, and antioxidant properties, as well as cardio-, hepato-, and neuroprotective features. Recent studies have shown that 20E may also possess antineoplastic activity. In the present study, we reveal the anticancer properties of 20E in Non-Small Cell Lung Cancer (NSCLC) cell lines. 20E displayed significant antioxidant capacities and induced the expression of antioxidative stress response genes. The RNA-seq analysis of 20E-treated lung cancer cells revealed the attenuation of genes involved in different metabolic processes. Indeed, 20E suppressed several enzymes of glycolysis and one-carbon metabolism, as well as their key transcriptional regulators—c-Myc and ATF4, respectively. Accordingly, using the SeaHorse energy profiling approach, we observed the inhibition of glycolysis and respiration mediated by 20E treatment. Furthermore, 20E sensibilized lung cancer cells to metabolic inhibitors and markedly suppressed the expression of Cancer Stem Cells (CSCs) markers. Thus, in addition to the known beneficial pharmacological activities of 20E, our data uncovered novel antineoplastic properties of 20E in NSCLC cells.

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“…A high expression of HK2 has been observed in the majority of tumors, and this increase in HK2 levels has been correlated with the progression of tumors. Additionally, HK2 expression has been related to immune cell infiltration, such as T follicular helper cells (Tfh) [10].…”

Section: Metabolic Changes Of Cancer Cellsmentioning

confidence: 99%

Immunological Aspects of Cancer Cell Metabolism

Ucche,

Hayakawa

2024

IJMS

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Cancer cells adeptly manipulate their metabolic processes to evade immune detection, a phenomenon intensifying the complexity of cancer progression and therapy. This review delves into the critical role of cancer cell metabolism in the immune-editing landscape, highlighting how metabolic reprogramming facilitates tumor cells to thrive despite immune surveillance pressures. We explore the dynamic interactions within the tumor microenvironment (TME), where cancer cells not only accelerate their glucose and amino acid metabolism but also induce an immunosuppressive state that hampers effective immune response. Recent findings underscore the metabolic competition between tumor and immune cells, particularly focusing on how this interaction influences the efficacy of emerging immunotherapies. By integrating cutting-edge research on the metabolic pathways of cancer cells, such as the Warburg effect and glutamine addiction, we shed light on potential therapeutic targets. The review proposes that disrupting these metabolic pathways could enhance the response to immunotherapy, offering a dual-pronged strategy to combat tumor growth and immune evasion.

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A pan-cancer analysis of the role of hexokinase II (HK2) in human tumors

Cited by 11 publications

References 42 publications

Cytotoxic Activity of Amaryllidaceae Plants against Cancer Cells: Biotechnological, In Vitro, and In Silico Approaches

Cytotoxic Activity of Amaryllidaceae Plants against Cancer Cells: Biotechnological, In Vitro, and In Silico Approaches

20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells

Immunological Aspects of Cancer Cell Metabolism

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