Type Iγ phosphatidylinositol phosphate kinase promotes tumor growth by facilitating Warburg effect in colorectal cancer

Peng, Wei; Huang, Wei; Ge, Xiaoxiao; Xue, Lu; Zhao, Wei; Xue, Junli

doi:10.1016/j.ebiom.2019.05.015

Cited by 22 publications

(26 citation statements)

References 43 publications

(63 reference statements)

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“…High expression of type Iγ phosphatidylinositol phosphate kinase (PIPKIγ) is more frequently observed in CRCs than in normal tissues and is associated with a poor clinical outcome. Upregulation of PIPKIγ in colorectal adenocarcinomas enhances their glycolysis and proliferative activity, whereas PIPKIγ knockdown has been shown to be associated with inhibition of the PI3K/Akt/mTOR/c-Myc-HIF1α signaling pathway [274]. PIPKIγ may also be an important factor in the regulation of inflammatory infiltration.…”

Section: Hypoxia and Glycolysismentioning

confidence: 99%

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

2020

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Background Tumor initiation and subsequent progression are usually long-term processes, spread over time and conditioned by diverse aspects. Many cancers develop on the basis of chronic inflammation; however, despite dozens of years of research, little is known about the factors triggering neoplastic transformation under these conditions. Molecular characterization of both pathogenetic states, i.e., similarities and differences between chronic inflammation and cancer, is also poorly defined. The secretory activity of tumor cells may change the immunophenotype of immune cells and modify the extracellular microenvironment, which allows the bypass of host defense mechanisms and seems to have diagnostic and prognostic value. The phenomenon of immunosuppression is also present during chronic inflammation, and the development of cancer, due to its duration, predisposes patients to the promotion of chronic inflammation. The aim of our work was to discuss the above issues based on the latest scientific insights. A theoretical mechanism of cancer immunosuppression is also proposed. Conclusions Development of solid tumors may occur both during acute and chronic phases of inflammation. Differences in the regulation of immune responses between precancerous states and the cancers resulting from them emphasize the importance of immunosuppressive factors in oncogenesis. Cancer cells may, through their secretory activity and extracellular transport mechanisms, enhance deterioration of the immune system which, in turn, may have prognostic implications.

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Section: Hypoxia and Glycolysismentioning

confidence: 99%

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

2020

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“…Cancer cells rely on the ‘Warburg effect’ for aerobic glycolysis, leading to the accumulation of high lactate concentrations, even under aerobic conditions (Peng et al., 2019 ). Although the presence of lactate in the tumor microenvironment (TME) was previously considered as metabolic waste, more recently, accumulating evidence has suggested that it acts as an important signaling molecule in the regulation of tumor metabolism and immunity (Zhang et al., 2019 ).…”

Section: Introductionmentioning

confidence: 99%

L-EGCG-Mn nanoparticles as a pH-sensitive MRI contrast agent

Jiang

Shang

et al. 2020

Drug Delivery

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This study aimed to synthesize and characterize L-epigallocatechin gallate (EGCG) complexed Mn 2þ nanoparticle (L-EGCG-Mn), a proof-of-concept pH-sensitive manganese core nanoparticle (NP), and compare its magnetic resonance (MR) properties with those of Gd-DTPA, both in vitro and in vivo. Reverse microemulsion was used to obtain the L-EGCG-Mn NPs. The physicochemical properties of L-EGCG-Mn were characterized using dynamic light scattering, transmission electron microscopy, and near-infrared fluorescence small animal live imaging. The in vitro relaxivity of L-EGCG-Mn incubated with different pH buffer solutions (pH ¼ 7.4, 6.8, 5.5) was evaluated. The T1-weighted MR imaging (MRI) properties were evaluated in vitro using hypoxic H22 cells as well as in H22 tumor-bearing mice. Cytotoxicity tests and histological analysis were performed to evaluate the safety of L-EGCG-Mn. L-EGCG-Mn showed good biocompatibility, stability, pH sensitivity, and tumor-targeting ability. Moreover, when the pH was decreased from 7.4 to 5.5, the r 1 relaxivity of L-EGCG-Mn was shown to gradually increase from 1.79 to 6.43 mM À1 Ás À1 . Furthermore, after incubation with L-EGCG-Mn for 4 h, the T1 relaxation time of hypoxic H22 cells was significantly lower than that of normoxic H22 cells (1788 ± 89 vs. 1982 ± 68 ms, p¼.041). The in vivo analysis showed that after injection, L-EGCG-Mn exhibited a higher MRI signal compared to Gd-DTPA in H22 tumor-bearing mice (p < .05). Furthermore, L-EGCG-Mn was found to have a good safety profile via cytotoxicity tests and histological analysis. L-EGCG-Mn has a good safety profile and pH sensitivity and may thus serve as a potential MRI contrast agent.

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“…Aerobic glycolysis is emerged as a fundamental contributor in the tumor occurrence and progression, and blocking aerobic glycolysis has been considered as a therapeutic strategy to inhibit tumorigenesis 30,31 . As StarBase v3.0 analysis showed, Ezrin was positively correlated with metabolism‐associated proteins.…”

Section: Discussionmentioning

confidence: 99%

Ezrin as a prognostic indicator regulates colon adenocarinoma progression through glycolysis

Wang

Yang

Wang

et al. 2020

J of Gastro and Hepatol

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Background and Aim Aerobic glycolysis (the Warburg effect) is a distinctive metabolic hallmark of colon adenocarcinoma. Ezrin was a member of the Ezrin–Radixin–Moesin protein family and has been found profoundly implicated in tumorigenesis. However, the specific functional roles of Ezrin in metabolic reprogramming of colon adenocarcinoma remain poorly characterized and need to be explored. Methods The expression of Ezrin in colon adenocarcinoma tissues was screened by bioinformatics analysis and immunohistochemical assay. Si‐RNA‐mediated transfection and overexpression plasmid transfection were performed in colon adenocarcinoma cells. The proliferation viability was measured using MTT, colony formation, and EdU assays. The migration ability was determined using wound healing and transwell assay. The expression of EMT markers and transcriptional factors was detected using immunofluorescence staining and western blot assays. Glucose uptake, lactate production, and ATP assay were performed to validate the effect of Ezrin on glycolysis‐mediated colon adenocarcinoma progression. Results Ezrin was upregulated in colon adenocarcinoma tissues and associated with poor survival. Ezrin stimulated colon adenocarcinoma cell proliferation, migration, and the process of EMT. Ezrin aroused significant increase in glucose uptake, lactate production, and ATP level in colon adenocarcinoma cells. Further investigations demonstrated that treatment with a glycolytic inhibitor 2‐deoxy‐d‐glucose reversed the effects reduced by Ezrin on colon adenocarcinoma cells. Conclusions Our results evidenced a novel mechanism for colon adenocarcinoma cells proliferation and migration induced by Ezrin via glycolysis.

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Type Iγ phosphatidylinositol phosphate kinase promotes tumor growth by facilitating Warburg effect in colorectal cancer

Cited by 22 publications

References 43 publications

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

L-EGCG-Mn nanoparticles as a pH-sensitive MRI contrast agent

Ezrin as a prognostic indicator regulates colon adenocarinoma progression through glycolysis

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