iASPP is essential for HIF-1α stabilization to promote angiogenesis and glycolysis via attenuating VHL-mediated protein degradation

Dong, Zhao; Zheng, S.; Wang, Xingwen; Liu, Hao; Zhao, Kunming; Li, Li; Hu, Ying

doi:10.1038/s41388-022-02234-9

Cited by 6 publications

(5 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HIF-1α, a key transcription factor that regulates the expression of multiple downstream genes in a hypoxic environment after tissue injury, has been demonstrated to be extensively involved in glycolytic metabolism [84,85]. Previous studies have reported that deletion of VHL, a component of the E3 ubiquitin ligase complex that binds to HIF-1α and leads to its polyubiquitination of the α subunit and degradation by the proteasome under normoxic conditions, strengthens HIF-1α stabilization and accumulation to promote glycolysis and angiogenesis [35,86,87].…”

Section: Discussionmentioning

confidence: 99%

“…Hypoxia-induced factors alpha (HIF-1α), a transcriptional factor responsible for mediating glycolysis in the hypoxic microenvironment of the injury site [34,35], was assayed in injury-site sciatic nerve segments and HUVECs at the transcriptional and translational level. The findings revealed that the mRNA and protein expression of HIF-1α significantly increased after SCI and was counteracted by the local injection of GW4869 (Fig.…”

Section: Mir-21-5p Regulates Endothelial Metabolic Programming Via Ta...mentioning

confidence: 99%

See 1 more Smart Citation

Enhancing intraneural revascularization following peripheral nerve injury through hypoxic Schwann-cell-derived exosomes: an insight into endothelial glycolysis

Sun,

Zeng,

et al. 2024

J Nanobiotechnol

View full text Add to dashboard Cite

Background Endothelial cell (EC)-driven intraneural revascularization (INRV) and Schwann cells-derived exosomes (SCs-Exos) both play crucial roles in peripheral nerve injury (PNI). However, the interplay between them remains unclear. We aimed to elucidate the effects and underlying mechanisms of SCs-Exos on INRV following PNI. Results We found that GW4869 inhibited INRV, as well as that normoxic SCs-Exos (N-SCs-Exos) exhibited significant pro-INRV effects in vivo and in vitro that were potentiated by hypoxic SCs-Exos (H-SCs-Exos). Upregulation of glycolysis emerged as a pivotal factor for INRV after PNI, as evidenced by the observation that 3PO administration, a glycolytic inhibitor, inhibited the INRV process in vivo and in vitro. H-SCs-Exos more significantly enhanced extracellular acidification rate/oxygen consumption rate ratio, lactate production, and glycolytic gene expression while simultaneously suppressing acetyl-CoA production and pyruvate dehydrogenase E1 subunit alpha (PDH-E1α) expression than N-SCs-Exos both in vivo and in vitro. Furthermore, we determined that H-SCs-Exos were more enriched with miR-21-5p than N-SCs-Exos. Knockdown of miR-21-5p significantly attenuated the pro-glycolysis and pro-INRV effects of H-SCs-Exos. Mechanistically, miR-21-5p orchestrated EC metabolism in favor of glycolysis by targeting von Hippel-Lindau/hypoxia-inducible factor-1α and PDH-E1α, thereby enhancing hypoxia-inducible factor-1α-mediated glycolysis and inhibiting PDH-E1α-mediated oxidative phosphorylation. Conclusion This study unveiled a novel intrinsic mechanism of pro-INRV after PNI, providing a promising therapeutic target for post-injury peripheral nerve regeneration and repair. Graphical Abstract

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Mir-21-5p Regulates Endothelial Metabolic Programming Via Ta...mentioning

confidence: 99%

Enhancing intraneural revascularization following peripheral nerve injury through hypoxic Schwann-cell-derived exosomes: an insight into endothelial glycolysis

Sun,

Zeng,

et al. 2024

J Nanobiotechnol

View full text Add to dashboard Cite

show abstract

“…LKB1 , PTEN , and VHL are other tumor suppressor genes that modulate metabolic pathways by promoting glycolysis, inhibiting OXPHOS, and inhibiting lipid synthesis, along with many other metabolic alterations with the goal to suppress tumor growth. [ 37 , 58 – 60 ]…”

Section: Cross Talk Between Molecular Signaling and Metabolic Pathwaysmentioning

confidence: 99%

Targeting Cancer Metabolism to Improve Outcomes with Immune Checkpoint Inhibitors

Fatima

Abonofal

Stephen

2023

Journal of Immunotherapy and Precision Oncology

View full text Add to dashboard Cite

Immune checkpoint inhibitors have revolutionized the treatment paradigm of several cancers. However, not all patients respond to treatment. Tumor cells reprogram metabolic pathways to facilitate growth and proliferation. This shift in metabolic pathways creates fierce competition with immune cells for nutrients in the tumor microenvironment and generates by-products harmful for immune cell differentiation and growth. In this review, we discuss these metabolic alterations and the current therapeutic strategies to mitigate these alterations to metabolic pathways that can be used in combination with checkpoint blockade to offer a new path forward in cancer management.

show abstract

“…In the study by Andrea L Casillas et al [ 77 ], PIM1 kinase directly phosphorylated HIF-1α regardless of oxygen tension to prevent PHDs from binding to and hydroxylating HIF-1α, hence interrupting its degradation pathway. Dong Zhao et al [ 78 ] discovered that the oncogene iASPP (inhibitor of apoptosis-simulating protein of p53) bound directly to VHL and prevented HIF-1α from degrading without affecting the PHD-mediated HIF-1α hydroxylation. In conclusion, the fact that the HIF pathway is regulated by a variety of cellular conditions highlights the importance of this pathway in numerous biological processes.…”

Section: Hypoxic Tumor Microenvironmentmentioning

confidence: 99%

The hypoxia-driven crosstalk between tumor and tumor-associated macrophages: mechanisms and clinical treatment strategies

Bai

Jian

et al. 2022

Mol Cancer

View full text Add to dashboard Cite

Given that hypoxia is a persistent physiological feature of many different solid tumors and a key driver for cancer malignancy, it is thought to be a major target in cancer treatment recently. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME), which have a large impact on tumor development and immunotherapy. TAMs massively accumulate within hypoxic tumor regions. TAMs and hypoxia represent a deadly combination because hypoxia has been suggested to induce a pro-tumorigenic macrophage phenotype. Hypoxia not only directly affects macrophage polarization, but it also has an indirect effect by altering the communication between tumor cells and macrophages. For example, hypoxia can influence the expression of chemokines and exosomes, both of which have profound impacts on the recipient cells. Recently, it has been demonstrated that the intricate interaction between cancer cells and TAMs in the hypoxic TME is relevant to poor prognosis and increased tumor malignancy. However, there are no comprehensive literature reviews on the molecular mechanisms underlying the hypoxia-mediated communication between tumor cells and TAMs. Therefore, this review has the aim to collect all recently available data on this topic and provide insights for developing novel therapeutic strategies for reducing the effects of hypoxia.

show abstract

iASPP is essential for HIF-1α stabilization to promote angiogenesis and glycolysis via attenuating VHL-mediated protein degradation

Cited by 6 publications

References 54 publications

Enhancing intraneural revascularization following peripheral nerve injury through hypoxic Schwann-cell-derived exosomes: an insight into endothelial glycolysis

Enhancing intraneural revascularization following peripheral nerve injury through hypoxic Schwann-cell-derived exosomes: an insight into endothelial glycolysis

Targeting Cancer Metabolism to Improve Outcomes with Immune Checkpoint Inhibitors

The hypoxia-driven crosstalk between tumor and tumor-associated macrophages: mechanisms and clinical treatment strategies

Contact Info

Product

Resources

About