The type 1 transmembrane glycoprotein B7‐H3 interacts with the glycolytic enzyme <scp>ENO</scp>1 to promote malignancy and glycolysis in HeLa cells

Zuo, Jiane; Wang, Bowen; Long, Min; Gao, Zhaowei; Zhang, Zhe; Wang, Huiping; Wang, Xi; Li, Ruicheng; Dong, Ke; Zhang, Huizhong

doi:10.1002/1873-3468.13164

Cited by 23 publications

(20 citation statements)

References 26 publications

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“…Moreover, accelerated glycolysis increases the proliferation and invasion of non-small cell lung cancer 31 . Previous studies have demonstrated that the enhancement of aerobic glycolysis markedly promotes cancer cell growth and development 32,53,54 . However, studies focused on the association of glycolysis levels and stem-like characteristics of GC cells are scarce to nonexistent.…”

Section: Discussionmentioning

confidence: 99%

Enolase 1 regulates stem cell-like properties in gastric cancer cells by stimulating glycolysis

et al. 2020

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Recent studies have demonstrated that gastric cancer stem cells (CSCs) are a rare sub-group of gastric cancer (GC) cells and have an important role in promoting the tumor growth and progression of GC. In the present study, we demonstrated that the glycolytic enzyme Enolase 1 (ENO1) was involved in the regulation of the stem cell-like characteristics of GC cells, as compared to the parental cell lines PAMC-82 and SNU16, the expression of ENO1 in spheroids markedly increased. We then observed that ENO1 could enhance stem cell-like characteristics, including self-renewal capacity, cell invasion and migration, chemoresistance, and even the tumorigenicity of GC cells. ENO1 is known as an enzyme that is involved in glycolysis, but our results showed that ENO1 could markedly promote the glycolytic activity of cells. Furthermore, inhibiting glycolysis activity using 2-deoxy-d-glucose treatment significantly reduced the stemness of GC cells. Therefore, ENO1 could improve the stemness of CSCs by enhancing the cells’ glycolysis. Subsequently, to further confirm our results, we found that the inhibition of ENO1 using AP-III-a4 (ENOblock) could reduce the stemness of GC cells to a similar extent as the knockdown of ENO1 by shRNA. Finally, increased expression of ENO1 was related to poor prognosis in GC patients. Taken together, our results demonstrated that ENO1 is a significant biomarker associated with the stemness of GC cells.

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Section: Discussionmentioning

confidence: 99%

Enolase 1 regulates stem cell-like properties in gastric cancer cells by stimulating glycolysis

et al. 2020

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“…Moreover, accelerated glycolysis increases the proliferation and invasion of non-small cell lung cancer [31]. Previous studies have demonstrated that enhancement of aerobic glycolysis markedly promotes cancer cells growth and development [32,53,54]. However, studies focused on the association of glycolysis levels and stem-like characteristics of GC cells are scarce to nonexistent.…”

Section: Discussionmentioning

confidence: 99%

“…For example, overexpression of ENO1 can promote tumor growth in hepatocellular carcinoma, and head and neck cancers, and functions as a potential oncogenic factor [29,30]. Furthermore, ENO1 was shown to in uence proliferation, metastasis and drug resistance in cancer cells by participating in the Warburg effect [31,32]. These studies indicated that ENO1 functioned as a potential oncogenic factor in endometrial carcinoma by inducing glycolysis [33].…”

Section: Read Full Licensementioning

confidence: 99%

Enolase 1 Regulates Stem Cell-Like Properties in Gastric Cancer Cells by Stimulating Glycolysis

Yang

Xiong

Zhang

et al. 2020

Preprint

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Abstract Background: Recent studies have demonstrated that gastric cancer stem cells (CSCs) are a rare sub-group of gastric cancer (GC) cells and play an important role in promoting the tumor growth and progression of GC. In the present study, we demonstrated that the glycolytic enzyme Enolase 1 (ENO1) was involved in the regulation of the stem cell-like characteristics of GC cells.Methods: Self-renewal, Chemosensitivity and invasion of GC cells were evaluated by sphere formation, Chemosensitivity assay and invasion assay respectively. Glycolysis level was examined by the Seahorse XFe/XF Analyzer. ENO1 expression was determined in 83 GC specimens by immunohistochemistry. Results: The expression of ENO1 in sphere cells markedly increased as compared to the parental cell lines PAMC-82 and SNU16. We then observed that ENO1 could enhance stem cell-like characteristics, including self-renewal capacity, cell invasion and migration, chemoresistance, and even the tumorigenicity of GC cells. ENO1 is known as an enzyme that is involved in glycolysis, and our results showed that ENO1 could markedly promote the glycolytic activity of cells. Furthermore, inhibiting glycolysis activity using 2-Deoxy-D-glucose treatment significantly reduced the stemness of GC cells. Therefore, ENO1 could improve the stemness of CSCs by enhancing the cells’ glycolysis. Subsequently, to further confirm our results, we found that the inhibition of ENO1 using AP-III-a4 (ENOblock) could reduce the stemness of GC cells to a similar extent as the knockdown of ENO1 by shRNA. Finally, increased expression of ENO1 was related with poor prognosis in GC patients. Conclusion: Taken together, our results demonstrated that ENO1 is a significant biomarker associated with the stemness of GC cells.

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“…Interestingly, hexokinase 1 and 2 (HK2) were also observed in both control and B7-H3 OE exosomes. A previous publication investigated the relationship between B7-H3 and ENO1, finding that downregulation of B7-H3 leads to a downregulation of ENO1 and subsequent impairment of glycolysis in HeLa cells [ 64 ]. Another study indicated that B7-H3 may promote glycolysis by upregulating HK2 [ 65 ].…”

Section: Discussionmentioning

confidence: 99%

B7-H3 in Medulloblastoma-Derived Exosomes; A Novel Tumorigenic Role

Purvis

Velpula

Guda

et al. 2020

IJMS

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(1) Aim: Medulloblastoma is the most common aggressive pediatric cancer of the central nervous system. Improved therapies are necessary to improve life outcomes for medulloblastoma patients. Exosomes are a subset of extracellular vesicles that are excreted outside of the cell, and can transport nucleic acids and proteins from donor cells to nearby recipient cells of the same or dissimilar tissues. Few publications exist exploring the role that exosomes play in medulloblastoma pathogenesis. In this study, we found B7-H3, an immunosuppressive immune checkpoint, present in D283 cell-derived exosomes. (2) Methods: Utilizing mass spectrometry and immunoblotting, the presence of B7-H3 in D283 control and B7-H3 overexpressing exosomes was confirmed. Exosomes were isolated by Systems Biosciences from cultured cells as well as with an isolation kit that included ultracentrifugation steps. Overlay experiments were performed to determine mechanistic impact of exosomes on recipient cells by incubating isolated exosomes in serum-free media with target cells. Impact of D283 exosome incubation on endothelial and UW228 medulloblastoma cells was assessed by immunoblotting. Immunocytochemistry was employed to visualize exosome fusion with recipient cells. (3) Results: Overexpressing B7-H3 in D283 cells increases exosomal production and size distribution. Mass spectrometry revealed a host of novel, pathogenic molecules associated with B7-H3 in these exosomes including STAT3, CCL5, MMP9, and PI3K pathway molecules. Additionally, endothelial and UW228 cells incubated with D283-derived B7-H3-overexpressing exosomes induced B7-H3 expression while pSTAT1 levels decreased in UW228 cells. (4) Conclusions: In total, our results reveal a novel role in exosome production and packaging for B7-H3 that may contribute to medulloblastoma progression.

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The type 1 transmembrane glycoprotein B7‐H3 interacts with the glycolytic enzyme ENO1 to promote malignancy and glycolysis in HeLa cells

Cited by 23 publications

References 26 publications

Enolase 1 regulates stem cell-like properties in gastric cancer cells by stimulating glycolysis

Enolase 1 regulates stem cell-like properties in gastric cancer cells by stimulating glycolysis

Enolase 1 Regulates Stem Cell-Like Properties in Gastric Cancer Cells by Stimulating Glycolysis

B7-H3 in Medulloblastoma-Derived Exosomes; A Novel Tumorigenic Role

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