Effect of GLUT1 Inhibition and Autophagy Modulation on the Growth and Migration of Laryngeal Carcinoma Stem Cells Under Hypoxic and Low-Glucose Conditions

Chen, Xiaohong; Liu, Jia; Zhong, Jiang-Tao; Zhou, Shui‐Hong; Fan, Jun

doi:10.2147/ott.s300423

Cited by 12 publications

(16 citation statements)

References 41 publications

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“…This approach not only expands our understanding of BAY-876 antitumor activity, but also provides a new strategy for research of water insoluble drugs. Moreover, an aberrant metabolism characterized by impaired glucose uptake or by aerobic glycolysis is associated with the overexpression of GLUT1 (58)(59)(60)(61)(62)(63). The aberrant metabolism of HCC cells also participates in the progression of HCC by influencing the tumor microenvironment (14,(64)(65)(66)(67).…”

Section: Discussionmentioning

confidence: 99%

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A Novel Microcrystalline BAY-876 Formulation Achieves Long-Acting Antitumor Activity Against Aerobic Glycolysis and Proliferation of Hepatocellular Carcinoma

et al. 2021

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BAY-876 is an effective antagonist of the Glucose transporter type 1 (GLUT1) receptor, a mediator of aerobic glycolysis, a biological process considered a hallmark of hepatocellular carcinoma (HCC) together with cell proliferation, drug-resistance, and metastasis. However, the clinical application of BAY-876 has faced many challenges. In the presence study, we describe the formulation of a novel microcrystalline BAY-876 formulation. A series of HCC tumor models were established to determine not only the sustained release of microcrystalline BAY-876, but also its long-acting antitumor activity. The clinical role of BAY-876 was confirmed by the increased expression of GLUT1, which was associated with the worse prognosis among advanced HCC patients. A single dose of injection of microcrystalline BAY-876 directly in the HCC tissue achieved sustained localized levels of Bay-876. Moreover, the single injection of microcrystalline BAY-876 in HCC tissues not only inhibited glucose uptake and prolonged proliferation of HCC cells, but also inhibited the expression of epithelial-mesenchymal transition (EMT)-related factors. Thus, the microcrystalline BAY-876 described in this study can directly achieve promising localized effects, given its limited diffusion to other tissues, thereby reducing the occurrence of potential side effects, and providing an additional option for advanced HCC treatment.

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Section: Discussionmentioning

confidence: 99%

“…Moreover, an aberrant metabolism characterized by impaired glucose uptake or by aerobic glycolysis is associated with the overexpression of GLUT1 ( 58 – 63 ). The aberrant metabolism of HCC cells also participates in the progression of HCC by influencing the tumor microenvironment ( 14 , 64 – 67 ).…”

Section: Discussionmentioning

confidence: 99%

A Novel Microcrystalline BAY-876 Formulation Achieves Long-Acting Antitumor Activity Against Aerobic Glycolysis and Proliferation of Hepatocellular Carcinoma

et al. 2021

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“…Hypoxia, the most important factor leading to the metabolic reprogramming and induction of CSCs, is shown to induce GLUT1, the transporter of glucose into cells ( 77 , 78 ). The metabolic reprogramming in CSCs is shown to be dependent on GLUT1 in many cancer types ( 6 , 79 – 81 ). Remarkably, GLUT1 is shown to interact with βIVb-tubulin in glioblastoma specimens using mass spectrometric analysis, which was confirmed again by proximity ligation assay and immunoprecipitation ( 6 ).…”

Section: Tubulins Implicated In the Regulation Of Cscs And Their Nichementioning

confidence: 99%

Tubulin Isotypes: Emerging Roles in Defining Cancer Stem Cell Niche

2022

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Although the role of microtubule dynamics in cancer progression is well-established, the roles of tubulin isotypes, their cargos and their specific function in the induction and sustenance of cancer stem cells (CSCs) were poorly explored. But emerging reports urge to focus on the transport function of tubulin isotypes in defining orchestrated expression of functionally critical molecules in establishing a stem cell niche, which is the key for CSC regulation. In this review, we summarize the role of specific tubulin isotypes in the transport of functional molecules that regulate metabolic reprogramming, which leads to the induction of CSCs and immune evasion. Recently, the surface expression of GLUT1 and GRP78 as well as voltage-dependent anion channel (VDAC) permeability, regulated by specific isotypes of β-tubulins have been shown to impart CSC properties to cancer cells, by implementing a metabolic reprogramming. Moreover, βIVb tubulin is shown to be critical in modulating EphrinB1signaling to sustain CSCs in oral carcinoma. These tubulin-interacting molecules, Ephrins, GLUT1 and GRP78, are also important regulators of immune evasion, by evoking PD-L1 mediated T-cell suppression. Thus, the recent advances in the field implicate that tubulins play a role in the controlled transport of molecules involved in CSC niche. The indication of tubulin isotypes in the regulation of CSCs offers a strategy to specifically target those tubulin isotypes to eliminate CSCs, rather than the general inhibition of microtubules, which usually leads to therapy resistance.

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“…14,15 Autophagy is implicated in tumorigenesis 16 ; it also contributes to cell proliferation and the chemoradiosensitivity of laryngeal carcinoma, [17][18][19] as well as the adaptation of laryngeal carcinoma cells to hypoxic, low-glucose conditions. 20 However, the role of autophagy in the proliferation of VCL cells remains unclear.…”

mentioning

confidence: 99%

“…Through regulation of autophagy flux, H + /K + ATPase plays a role in the acidification of lysosomes that is similar to the role of vacuolar‐type H + ‐ATPase (V‐ATPase) 14,15 . Autophagy is implicated in tumorigenesis 16 ; it also contributes to cell proliferation and the chemoradiosensitivity of laryngeal carcinoma, 17‐19 as well as the adaptation of laryngeal carcinoma cells to hypoxic, low‐glucose conditions 20 . However, the role of autophagy in the proliferation of VCL cells remains unclear.…”

mentioning

confidence: 99%

Pepsin Increases the Proliferation of Vocal Cord Leukoplakia Epithelial Cells by Inducing Autophagy

Chen

Zhang

Jiang

et al. 2023

Otolaryngol.--head neck surg.

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ObjectiveTo investigate the role of H+/K+ATPase in the proliferation of pepsin‐induced vocal cord leukoplakia (VCL) cells.Study DesignTranslation research.SettingAffiliated Hospital of University.MethodsImmunohistochemistry was used to detect pepsin, H+/K+ATPase (ATP4A and ATP4B subunits) in VCL cells with varying degrees of dysplasia. After primary cultures of VCL cells had been established, the effects of acidified pepsin on the proliferation, autophagy, and H+/K+‐ATPase distribution of VCL cells were investigated.ResultsThe levels of pepsin, ATP4A, and ATP4B were significantly higher in VCL tissue with moderate‐to‐severe dysplasia than in normal tissue (p < .05); these levels gradually increased according to dysplasia severity. The expression levels of ATP4A and ATP4B were significantly correlated with the amount of pepsin in VCL cells (p < .01). Acidified pepsin enhanced the levels of proliferation and autophagy in human VCL epithelial cells. The cloning‐ and autophagy‐promoting effects of acidified pepsin on VCL cells were partially reversed by pantoprazole; these effects were completely blocked by the autophagy inhibitor chloroquine. Finally, acidified pepsin promoted the colocalization of H+/K+‐ATPase and lysosomes in VCL cells; it also mediated lysosome acidification.ConclusionPepsin and H+/K+‐ATPase may contribute to the progression of VCL. Specifically, acidified pepsin may regulate lysosome acidification by promoting lysosomal localization of H+/K+‐ATPase.

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Effect of GLUT1 Inhibition and Autophagy Modulation on the Growth and Migration of Laryngeal Carcinoma Stem Cells Under Hypoxic and Low-Glucose Conditions

Cited by 12 publications

References 41 publications

A Novel Microcrystalline BAY-876 Formulation Achieves Long-Acting Antitumor Activity Against Aerobic Glycolysis and Proliferation of Hepatocellular Carcinoma

A Novel Microcrystalline BAY-876 Formulation Achieves Long-Acting Antitumor Activity Against Aerobic Glycolysis and Proliferation of Hepatocellular Carcinoma

Tubulin Isotypes: Emerging Roles in Defining Cancer Stem Cell Niche

Pepsin Increases the Proliferation of Vocal Cord Leukoplakia Epithelial Cells by Inducing Autophagy

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