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Cited by 505PI3K/AKT/mTOR signaling in cancerErythropoietin and Anemia TreatmentCancer, Hypoxia, and Metabolism

PI3K/Akt signaling transduction pathway, erythropoiesis and glycolysis in hypoxia (Review)

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Xie, Youbang, Shi, Xuefeng, Sheng, Kuo, Han, Guoxiong, Li, Wenqian, Zhao, Qiangqiang, Jiang, Baili, Feng, Jianming +2 more·2018·Molecular Medicine Reports
DOI 10.3892/mmr.2018.9713PMC PMC6323245
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Abstract

The purpose of this review is to summarize the research progress of PI3K/Akt signaling pathway in erythropoiesis and glycolysis. Phosphatidylinositol‑4,5‑bisphosphate 3‑kinase (PI3K) is activated by numerous genes and leads to protein kinase B (Akt) binding to the cell membrane, with the help of phosphoinositide‑dependent kinase, in the PI3K/Akt signal transduction pathway. Threonine and serine phosphorylation contribute to Akt translocation from the cytoplasm to the nucleus and further mediates enzymatic biological effects, including those involved in cell proliferation, apoptosis inhibition, cell migration, vesicle transport and cell cancerous transformation. As a key downstream protein of the PI3K/Akt signaling pathway, hypoxia‑inducible factor (HIF)‑1 is closely associated with the concentration of oxygen in the environment. Maintaining stable levels of HIF‑1 protein is critical under normoxic conditions; however, HIF‑1 levels quickly increase under hypoxic conditions. HIF‑1α is involved in the acute hypoxic response associated with erythropoietin, whereas HIF‑2α is associated with the response to chronic hypoxia. Furthermore, PI3K/Akt can reduce the synthesis of glycogen and increase glycolysis. Inhibition of glycogen synthase kinase 3β activity by phosphorylation of its N‑terminal serine increases accumulation of cyclin D1, which promotes the cell cycle and improves cell proliferation through the PI3K/Akt signaling pathway. The PI3K/Akt signaling pathway is closely associated with a variety of enzymatic biological effects and glucose metabolism.

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  • PI3K/Akt effects on glucose metabolism are also mediated via HIF-independent mechanisms.

    “While the effect of the PI3K/Akt signalling pathway on glycolysis has been shown to be mediated in part via its regulation of HIF-1α expression and transcriptional activity in hypoxia [133,134], several lines of evidence have shown that its effects on glucose metabolism are also mediated via HIF-independent mechanisms.”

    From HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells (2021) · cites this paper as [100]

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Cited by

Sorted by citations

Authors
Xie, Y., Shi, X., Sheng, K., Han, G., Li, W., Zhao, Q., Jiang, B., Feng, J., Li, J., & Gu, Y.
Affiliations
  • Qinghai Provincial Peoples Hospital (CN)
  • Department of Hematology, Qinghai Provincial People's Hospital, Xining, Qinghai 810007, P.R. China
Corresponding author
  • Li, Jianping
  • Gu, Yuhai
ORCID
Venue
Molecular Medicine Reports
Publisher
Spandidos Publications
Published
2018-12-03
Volume
19
Issue
2
Pages
783-791
ISSN
  • 1791-2997 (ISSN-L)
  • 1791-3004
DOI
10.3892/mmr.2018.9713
PMC
PMC6323245
OpenAlex
W2902256938
Cited by
505
References
8
Citations by year
2026: 15 · 2025: 63 · 2024: 112 · 2023: 101 · 2022: 116 · 2021: 55 · 2020: 33 · 2019: 10
FWCI
2.40
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Molecular Medicine Reports (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (81360084)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords
PI3K/Akt signaling, erythropoiesis, hypoxia, glycolysis, HIF-1, HIF-1α, HIF-2α, erythropoietin, glycogen synthase kinase-3β, cyclin D1, glucose metabolism, Akt phosphorylation, cell proliferation
MeSH terms
Animals, Hypoxia, Erythropoiesis, Glycolysis, Humans, Signal Transduction, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt

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