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Review

Advances in semaphorin 3B research in tumors (Review)

  • Authors:
    • Xue Zhang
    • Ruizeng Feng
    • Huanfen Zhao
    • Jie Wei
    • Xing Xu
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, The First People's Hospital of Xiantao, Affiliated Hospital of Hubei University of Science and Technology, Xiantao, Hubei 433000, P.R. China, Department of Hepatobiliary Surgery, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China, Department of Pathology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China, Department of Gastrointestinal Surgery, The First People's Hospital of Xiantao, Affiliated Hospital of Hubei University of Science and Technology, Xiantao, Hubei 433000, P.R. China
  • Article Number: 25
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    Published online on: February 17, 2026
       https://doi.org/10.3892/mco.2026.2934
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Abstract

Advancing precision oncology has driven breakthroughs in understanding oncogenes, tumor suppressors, signaling pathway regulation, apoptosis, and cell cycle control. Molecularly targeted therapies, now integral to malignant tumor treatment, exploit these insights. Functioning as a tumor suppressor, semaphorin 3B (SEMA3B) is frequently inactivated across malignancies via promoter hypermethylation, loss of heterozygosity, and proteolytic cleavage. Its structure‑function relies on receptor complex formation, enabling activation of multiple pathways that induce tumor cell apoptosis, arrest the cell cycle, and competitively inhibit vascular endothelial growth factor‑binding to neuropilin 1. This blockade of the PI3K/Akt pathway suppresses tumor angiogenesis, metastasis, and proliferation. Therefore, comprehensively elucidating SEMA3B and its interactors is crucial for identifying novel biomarkers for early cancer detection and molecular therapeutic targets. Future research should focus on translating these findings into clinical applications, including the development of SEMA3B‑based epigenetic therapies and combination strategies with anti‑angiogenic agents. Key challenges remain in fully delineating the context‑dependent dual roles of SEMA3B, understanding its complex interactions within the tumor microenvironment, and overcoming its inactivation mechanisms for effective therapeutic restoration.
View Figures

Figure 1

Schematic overview of SEMA3B
signaling and inactivation mechanisms in tumors. Left panel: SEMA3B
binds to NRP1/2 and plexin receptors, inhibiting PI3K/Akt signaling
and competing with VEGF for NRP1 binding, leading to suppression of
tumor progression. Right panel: SEMA3B is inactivated through
promoter hypermethylation, proteolytic cleavage by furin-like
proteases, and loss of heterozygosity at 3p21.3. SEMA3B, semaphorin
3B; NRP, neuropilin; VEGF, vascular endothelial growth factor;
VEGFR2, VEGF receptor 2; MVD, microvessel density; DNMTs, DNA
methyltransferases; MBD, methyl-CpG binding domain.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang X, Feng R, Zhao H, Wei J and Xu X: Advances in semaphorin 3B research in tumors (Review). Mol Clin Oncol 24: 25, 2026.
APA
Zhang, X., Feng, R., Zhao, H., Wei, J., & Xu, X. (2026). Advances in semaphorin 3B research in tumors (Review). Molecular and Clinical Oncology, 24, 25. https://doi.org/10.3892/mco.2026.2934
MLA
Zhang, X., Feng, R., Zhao, H., Wei, J., Xu, X."Advances in semaphorin 3B research in tumors (Review)". Molecular and Clinical Oncology 24.4 (2026): 25.
Chicago
Zhang, X., Feng, R., Zhao, H., Wei, J., Xu, X."Advances in semaphorin 3B research in tumors (Review)". Molecular and Clinical Oncology 24, no. 4 (2026): 25. https://doi.org/10.3892/mco.2026.2934
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang X, Feng R, Zhao H, Wei J and Xu X: Advances in semaphorin 3B research in tumors (Review). Mol Clin Oncol 24: 25, 2026.
APA
Zhang, X., Feng, R., Zhao, H., Wei, J., & Xu, X. (2026). Advances in semaphorin 3B research in tumors (Review). Molecular and Clinical Oncology, 24, 25. https://doi.org/10.3892/mco.2026.2934
MLA
Zhang, X., Feng, R., Zhao, H., Wei, J., Xu, X."Advances in semaphorin 3B research in tumors (Review)". Molecular and Clinical Oncology 24.4 (2026): 25.
Chicago
Zhang, X., Feng, R., Zhao, H., Wei, J., Xu, X."Advances in semaphorin 3B research in tumors (Review)". Molecular and Clinical Oncology 24, no. 4 (2026): 25. https://doi.org/10.3892/mco.2026.2934
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