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Review Open Access

Molecular mechanisms and functions of guanylate‑binding protein 2 in inflammation and cancer (Review)

  • Authors:
    • Zeyu Liu
    • Shijun Peng
    • Jia Ouyang
  • View Affiliations / Copyright

    Affiliations: School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100083, P.R. China, Department of Neurosurgery, Peking University People's Hospital, Beijing 100044, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 534
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    Published online on: September 18, 2025
       https://doi.org/10.3892/ol.2025.15280
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Abstract

The present review article aimed to summarize currently available research data on the roles and functions of human guanylate‑binding protein 2 (hGBP2) and murine (m)GBP2 in cancer and inflammation. In addition, its structure, hydrolytic mechanisms and molecular regulatory mechanisms are discussed. hGBP2 and mGBP2 are strongly induced by IFN‑γ through the IFN‑sensitive response element and IFN‑γ activation site sequences on their corresponding genes, whilst also being regulated by IFN‑α, IFN‑β and multiple STAT‑IFN‑regulatory factor complexes. In inflammation, hGBP2 primarily regulates activation of the NLR family pyrin domain‑containing 3 and absent in melanoma 2 inflammasome pathways and therefore the induction of pyroptosis. By contrast, in cancer, hGBP2 serves a dual role, such that it can either promote cancer progression or suppress cancer development in a context‑dependent manner. This leads to variations in the hGBP2 expression profile across different cancer types in addition to their corresponding prognostic outcomes. hGBP2 can also respond to paclitaxel, a notable anticancer drug. The present review aims to summarize the structural basis and regulatory mechanisms of hGBP2, elucidate the roles of both hGBP2 and mGBP2 in inflammation and cancer and propose prospective research directions to inform future fundamental investigations and clinical applications.
View Figures

Figure 1

GBP2 gene regulation under basal
conditions (without IFN-I/II stimulation). GBP2, guanylate-binding
protein 2; GAS, γ-activated sequence; ISRE, IFN-stimulated response
element; IFNAR, IFN-α/β receptor; IFNGR, IFN-γ receptor; IRF,
IFN-regulatory factor; ISGF, IFN-stimulated gene factor.

Figure 2

GBP2 gene regulation upon IFN-I and
IFN-II stimulation. GBP2, guanylate-binding protein 2; GAS,
γ-activated sequence; ISRE, IFN-stimulated response element; IFNAR,
IFN-α/β receptor; IFNGR, IFN-γ receptor; IRF, IFN-regulatory
factor; ISGF, IFN-stimulated gene factor; JAK1, Janus kinase 1;
TYK2, tyrosine kinase 2.
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Copy and paste a formatted citation
Spandidos Publications style
Liu Z, Peng S and Ouyang J: Molecular mechanisms and functions of guanylate‑binding protein 2 in inflammation and cancer (Review). Oncol Lett 30: 534, 2025.
APA
Liu, Z., Peng, S., & Ouyang, J. (2025). Molecular mechanisms and functions of guanylate‑binding protein 2 in inflammation and cancer (Review). Oncology Letters, 30, 534. https://doi.org/10.3892/ol.2025.15280
MLA
Liu, Z., Peng, S., Ouyang, J."Molecular mechanisms and functions of guanylate‑binding protein 2 in inflammation and cancer (Review)". Oncology Letters 30.5 (2025): 534.
Chicago
Liu, Z., Peng, S., Ouyang, J."Molecular mechanisms and functions of guanylate‑binding protein 2 in inflammation and cancer (Review)". Oncology Letters 30, no. 5 (2025): 534. https://doi.org/10.3892/ol.2025.15280
Copy and paste a formatted citation
x
Spandidos Publications style
Liu Z, Peng S and Ouyang J: Molecular mechanisms and functions of guanylate‑binding protein 2 in inflammation and cancer (Review). Oncol Lett 30: 534, 2025.
APA
Liu, Z., Peng, S., & Ouyang, J. (2025). Molecular mechanisms and functions of guanylate‑binding protein 2 in inflammation and cancer (Review). Oncology Letters, 30, 534. https://doi.org/10.3892/ol.2025.15280
MLA
Liu, Z., Peng, S., Ouyang, J."Molecular mechanisms and functions of guanylate‑binding protein 2 in inflammation and cancer (Review)". Oncology Letters 30.5 (2025): 534.
Chicago
Liu, Z., Peng, S., Ouyang, J."Molecular mechanisms and functions of guanylate‑binding protein 2 in inflammation and cancer (Review)". Oncology Letters 30, no. 5 (2025): 534. https://doi.org/10.3892/ol.2025.15280
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