VDAC2 interacts with PFKP to regulate glucose metabolism and phenotypic reprogramming of glioma stem cells

Zhou, Kai; Yao, Yueliang; He, Zhicheng; Chen, Cong; Zhang, Xiaoning; Yang, Kai‐Di; Liu, Yuqi; Liu, Qing; Fu, Wen-Juan; Chen, Yaping; Niu, Qin; Ma, Qiang; Zhou, Rong; Yao, Xiaohong; Zhang, Xia; Cui, You‐Hong; Bian, Xiu‐Wu; Shi, Yu; Ping, Yi‐Fang

doi:10.1038/s41419-018-1015-x

Cited by 54 publications

(48 citation statements)

References 69 publications

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“…It induces mitochondrial dysfunction, release of ROS and ultimately promotes ferroptosis by directly binding to VDAC2 7 . High expression of VDAC2 was associated with a longer OS and negatively correlated with glioma grades 26 . DNAJB6 is an HSP40 family protein that has significant influence on the inhibition of tumour growth and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Ferroptosis‐related gene signature as a prognostic marker for lower‐grade gliomas

Zheng

Xie

et al. 2021

J Cellular Molecular Medi

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Ferroptosis is a newly discovered form of programmed cell death, which has unique biological effects on metabolism and redox biology. In this study, the prognostic value of ferroptosis‐related genes was investigated in lower‐grade gliomas (LGG). We downloaded the ferroptosis‐related genes from the FerrDb dataset. Univariate Cox and LASSO regression analyses were applied to identify genes correlated with overall survival (OS). Subsequently, 12 ferroptosis‐related genes were screened to establish the prognostic signature using stepwise multivariate Cox regression. According to the median value of risk scores, patients were divided into low‐ and high‐risk subgroups. The Kaplan‐Meier curves showed the high‐risk group had a lower OS. The predictive power of the risk model was validated using the CGGA. Functional analysis revealed that the terms associated with plasma membrane receptor complex, immune response and glutamate metabolic process were primarily related to the risk model. Moreover, we established a nomogram that had a strong forecasting ability for the 1‐, 3‐ and 5‐year OS. In addition, we compared the risk scores between different clinical features. We also detected infiltration of macrophages and monocytes in different subgroups. Overall, our study identified the prognostic signature of 12 ferroptosis‐related genes, which has the potential to predict the prognosis of LGG.

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Section: Discussionmentioning

confidence: 99%

Ferroptosis‐related gene signature as a prognostic marker for lower‐grade gliomas

Zheng

Xie

et al. 2021

J Cellular Molecular Medi

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“…At variance with this notion, CSCs show a unique metabolic adaptation that is determined by the surrounding environment, such as the hypoxic niche of solid tumors, regions with adequate levels of oxygen (normoxia), active growing regions of the tumor and metastatic sites [94, 95, 99–101]. In a few instances, this wide adaptation has generated controversial results: Vlashi et al [102] showed that glioma CSCs relied mainly on OXPHOS for energy supply, while other studies described that glioma CSCs are driven by a glycolytic reprogramming, exhibiting more fragmented mitochondria than neuronal stem cells and downregulation of mitochondrial respiratory activity in GSCs [103]. Although CSCs denote an elevated degree of metabolic plasticity, growing evidence suggests that these cells rely more on OXPHOS for energy production, with this being a far more efficient process in ATP generation than glycolysis (as recently reviewed in refs.…”

Section: Mitophagy In Cscs: a Role In Metabolic Reprogrammingmentioning

confidence: 99%

Autophagy and cancer stem cells: molecular mechanisms and therapeutic applications

et al. 2019

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Autophagy and mitophagy act in cancer as bimodal processes, whose differential functions strictly depend on cancer ontogenesis, progression, and type. For instance, they can act to promote cancer progression by helping cancer cells survive stress or, instead, when mutated or abnormal, to induce carcinogenesis by influencing cell signaling or promoting intracellular toxicity. For this reason, the study of autophagy in cancer is the main focus of many researchers and several clinical trials are already ongoing to manipulate autophagy and by this way determine the outcome of disease therapy. Since the establishment of the cancer stem cell (CSC) theory and the discovery of CSCs in individual cancer types, autophagy and mitophagy have been proposed as key mechanisms in their homeostasis, dismissal or spread, even though we still miss a comprehensive view of how and by which regulatory molecules these two processes drive cell fate. In this review, we will dive into the deep water of autophagy, mitophagy, and CSCs and offer novel viewpoints on possible therapeutic strategies, based on the modulation of these degradative systems. Facts • Autophagy plays a dual role in cancer as a tumor suppressor and promoter. • CSCs are usually characterized by a dysregulation of autophagy/mitophagy.

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“…Therefore, the findings at CSCs after compound 1 treatment of MDA-MB-231 cells, increased GM3, IV 6 Neu5Ac-nLc 4 Cer, GalNAc-GM1b, Gb 4 Cer, and GM2, could indicate CSC glycolysis slowdown. Cancer stem cells of glioma are more glycolytic than non-CSCs due to a mitochondrial voltage-dependent anion channel that controls the phenotype transition between glioma stem cells and non-stem cells 31 . The channel is highly expressed in non-CSC relative to CSC and coupled to a glycolytic rate-limiting enzyme platelet-type of phosphofructokinase on mitochondrion to inhibit kinase-mediated glycolysis required for CSC maintenance.…”

Section: Discussionmentioning

confidence: 99%

Glycosphingolipid expression at breast cancer stem cells after novel thieno[2,3-b]pyridine anticancer compound treatment

Marijan

Markotić

Mastelić

et al. 2020

Sci Rep

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Glycosphingolipid expression differs between human breast cancer stem cells (CSC) and cancer non-stem cells (non-CSC). We performed studies of viability, type of cell death, cancer stem cell percent and glycosphingolipid expression on CSC and non-CSC after treatment of MDA-MB-231 and MDA-MB-453 triple-negative breast cancer cells with a newly developed thienopyridine anticancer compound (3-amino-N-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide, 1). Compound 1 was cytotoxic for both breast cancer cell lines and the majority of cells died by treatment-induced apoptosis. The percent of cancer stem cells and number of formed mammospheres was significantly lower. Glycosphingolipids IV 6 Neu5Ac-nLc 4 Cer and GalNAc-GM1b (IV 3 Neu5Ac-Gg5Cer) not reported previously, were identified in both CSCs and non-CSCs. IV 6 Neu5Ac-nLc 4 Cer had increased expression in both CSCs and non-CSCs of both cell lines after the treatment with 1, while GM3 (II 3 Neu5Ac-LacCer) had increased expression only on both cell subpopulations in MDA-MB-231 cell line. GalNAc-GM1b, Gb 4 Cer (GalNAcβ1-3Galα1-4Galβ1-4Glcβ1-1Cer) and GM2 (II 3 Neu5Ac-GalNAcβ1-4Galβ1-4Glcβ1-1Cer) were increased only in CSCs of both cell lines while GD3 was decreased in CSC of MDA-MB-231 cell line. Due to its effect in reducing the percentage of cancer stem cells and number of mammospheres, and its influence upon several glycosphingolipid expressions, it can be concluded that compound 1 deserves attention as a potential new drug for triple-negative breast cancer therapy. The thieno[2,3-b]pyridines were initially discovered as potential inhibitors of phospholipase C (PLC) isoforms by virtual high throughput screen (vHTS) 1. Recently, we described glycoconjugate GM3 and CD15s expression in MDA-MB-231 triple negative breast cancer stem cell subpopulation cultured with 3-amino-5-oxo-N-naphthyl-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide, which was developed as a putative PLC inhibitor. A close structural analogue of 3-amino-N-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide, or compound 1 2 was chosen for this study due to its enhanced potency against the MDA-MB-231 cell line and its mechanism of action has been investigated 3,4. Due to their ability to self-renew and to regenerate the primary tumour phenotypic heterogeneity, cancer stem cells are important therapeutical targets 5. CSCs are defined with their CD44 + /CD24 − or CD133 + phenotype 6. It is believed that CSCs are involved in therapy resistance in various cancers, including triple-negative breast cancers, i.e., breast cancers that do not express the genes for estrogen receptor, progesterone receptor and the human epidermal growth factor receptor-2 7. Glycosphingolipids (GSLs), consisting of a hydrophobic ceramide and hydrophilic carbohydrate residues, are an important component of cell plasma membranes. They regulate numerous cellular processes like adhesion, proliferation, apoptosis, recognition, modulation of signal transduct...

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VDAC2 interacts with PFKP to regulate glucose metabolism and phenotypic reprogramming of glioma stem cells

Cited by 54 publications

References 69 publications

Ferroptosis‐related gene signature as a prognostic marker for lower‐grade gliomas

Ferroptosis‐related gene signature as a prognostic marker for lower‐grade gliomas

Autophagy and cancer stem cells: molecular mechanisms and therapeutic applications

Glycosphingolipid expression at breast cancer stem cells after novel thieno[2,3-b]pyridine anticancer compound treatment

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