{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T09:05:12Z","timestamp":1789376712749,"version":"build-2803163510"},"reference-count":117,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010211","name":"Jilin Provincial Education Department","doi-asserted-by":"publisher","award":["JJKH20190823KJ"],"award-info":[{"award-number":["JJKH20190823KJ"]}],"id":[{"id":"10.13039\/501100010211","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jilin University of Chemical Technology","award":["2026047"],"award-info":[{"award-number":["2026047"]}]},{"name":"Jilin University of Chemical Technology","award":["2021022"],"award-info":[{"award-number":["2021022"]}]},{"award":["2026047"],"award-info":[{"award-number":["2026047"]}],"id":[{"id":"https:\/\/ror.org\/03bvz5p76","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2021022"],"award-info":[{"award-number":["2021022"]}],"id":[{"id":"https:\/\/ror.org\/03bvz5p76","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Jilin Huada Science and Technology Transfer Center Co., Ltd.","award":["25139"],"award-info":[{"award-number":["25139"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Plexin-B1, Plexin-B2, and Plexin-B3 are members of the Plexin-B receptor family, which engage distinct class IV semaphorins as major ligands: Plexin-B1 binds SEMA4D, Plexin-B2 interacts with SEMA4C and SEMA4B, and Plexin-B3 has been reported to bind HSPA5, while all three may participate in non-redundant ligand\u2013receptor networks. Researchers have found receptors associated with neurological and malignant, immune-mediated, and cardiovascular diseases. However, this study strives to provide a comprehensive, cross-disciplinary synthesis of the context-specific functions of Plexin-B family members and to critically evaluate their emerging therapeutic potential across multiple disease domains. In a tumor- and context-dependent manner, Plexin-B1 and Plexin-B2 promote metastasis in glioblastoma, colorectal cancer, and triple-negative breast cancer (TNBC) through RhoA\/Rac1-dependent signaling, while Plexin-B3 exhibits dual roles, acting as a tumor suppressor in TNBC under hypoxic conditions yet promoting motility in pancreatic cancer. Plexin-B regulates neuroinflammation in Alzheimer\u2019s disease and T-cell regulation in asthma and other cardiovascular diseases via signals. This review positions the Plexin-B family as a promising yet functionally complex target for future precision medicine.<\/jats:p>","DOI":"10.3390\/life16091523","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T08:10:23Z","timestamp":1789373423000},"page":"1523","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Context-Dependent Roles of the Plexin-B Family Across Neurological, Oncological, Immune and Cardiovascular Disorders: Mechanisms and Therapeutic Implications"],"prefix":"10.3390","volume":"16","author":[{"given":"Jianli","family":"Xu","sequence":"first","affiliation":[{"name":"College of Biology and Food Engineering, Jilin University of Chemical Technology, Jilin 132022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nannan","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Biology and Food Engineering, Jilin University of Chemical Technology, Jilin 132022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Lao","sequence":"additional","affiliation":[{"name":"College of Biology and Food Engineering, Jilin University of Chemical Technology, Jilin 132022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Biology and Food Engineering, Jilin University of Chemical Technology, Jilin 132022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.cytogfr.2020.05.006","article-title":"Semaphorins in health and disease","volume":"57","author":"Fard","year":"2021","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1111\/pin.13270","article-title":"Class IV semaphorins in disease pathogenesis","volume":"72","author":"Nojima","year":"2022","journal-title":"Pathol. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"105999","DOI":"10.1016\/j.neubiorev.2024.105999","article-title":"Plexins: Navigating through the neural regulation and brain pathology","volume":"169","author":"Khan","year":"2025","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"593922","DOI":"10.2147\/CMAR.S593922","article-title":"Context-Dependent Dual Roles of the Plexin-B Family in Cancer Progression: Mechanisms and Therapeutic Implications","volume":"18","author":"Mao","year":"2026","journal-title":"Cancer Manag. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.conb.2020.12.014","article-title":"Semaphorins and Plexins in central nervous system patterning: The key to it all?","volume":"66","author":"Limoni","year":"2021","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e2402755121","DOI":"10.1073\/pnas.2402755121","article-title":"Molecular mechanisms of proteoglycan-mediated semaphorin signaling in axon guidance","volume":"121","author":"Nourisanami","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e13856","DOI":"10.7717\/peerj.13856","article-title":"Integrated bioinformatics analysis identifies the effects of Sema3A\/NRP1 signaling in oligodendrocytes after spinal cord injury in rats","volume":"10","author":"Hu","year":"2022","journal-title":"PeerJ"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Toledano, S., and Neufeld, G. (2023). Plexins as Regulators of Cancer Cell Proliferation, Migration, and Invasivity. Cancers, 15.","DOI":"10.3390\/cancers15164046"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.molmed.2023.07.009","article-title":"Mind the (guidance) signals! Translational relevance of semaphorins, plexins, and neuropilins in pancreatic cancer","volume":"29","author":"Fard","year":"2023","journal-title":"Trends Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"10098","DOI":"10.1038\/s41467-025-65095-2","article-title":"Plexin-B1 safeguards astrocyte agility and glial alignment to facilitate wound corralling and axon pathfinding in mouse spinal cord injury model","volume":"16","author":"Ni","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6663291","DOI":"10.1155\/2020\/6663291","article-title":"Neutrophil-Derived Semaphorin 4D Induces Inflammatory Cytokine Production of Endothelial Cells via Different Plexin Receptors in Kawasaki Disease","volume":"2020","author":"Huang","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8691534","DOI":"10.1155\/2020\/8691534","article-title":"Sema4D Aggravated LPS-Induced Injury via Activation of the MAPK Signaling Pathway in ATDC5 Chondrocytes","volume":"2020","author":"Lei","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1101\/gad.349063.121","article-title":"Macrophages facilitate peripheral nerve regeneration by organizing regeneration tracks through Plexin-B2","volume":"36","author":"Li","year":"2022","journal-title":"Genes Dev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1038\/s43018-025-00985-4","article-title":"Glioblastoma shift from bulk to infiltrative growth is guided by plexin-B2-mediated microglia alignment in invasive niches","volume":"6","author":"Kang","year":"2025","journal-title":"Nat. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1002\/dneu.22364","article-title":"Impaired cortical neurogenesis in plexin-B1 and -B2 double deletion mutant","volume":"76","author":"Daviaud","year":"2016","journal-title":"Dev. Neurobiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1038\/s42003-021-02905-5","article-title":"Publisher Correction: Essential roles of plexin-B3+ oligodendrocyte precursor cells in the pathogenesis of Alzheimer\u2019s disease","volume":"4","author":"Yu","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/s41523-022-00485-z","article-title":"Sensory nerves enhance triple-negative breast cancer invasion and metastasis via the axon guidance molecule PlexinB3","volume":"8","author":"Le","year":"2022","journal-title":"npj Breast Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.canlet.2019.04.013","article-title":"CD100-plexin-B1 induces epithelial-mesenchymal transition of head and neck squamous cell carcinoma and promotes metastasis","volume":"455","author":"Zhang","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"102318","DOI":"10.1016\/j.jchemneu.2023.102318","article-title":"Cleavage of semaphorin 4 C interferes with the neuroprotective effect of the semaphorin 4 C\/Plexin B2 pathway on experimental intracerebral hemorrhage in rats","volume":"132","author":"Li","year":"2023","journal-title":"J. Chem. Neuroanat."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/s41467-017-00341-w","article-title":"Semaphorin 4C Plexin-B2 signaling in peripheral sensory neurons is pronociceptive in a model of inflammatory pain","volume":"8","author":"Paldy","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"112164","DOI":"10.1016\/j.celrep.2023.112164","article-title":"Plexin-B3 expression stimulates MET signaling, breast cancer stem cell specification, and lung metastasis","volume":"42","author":"Zuo","year":"2023","journal-title":"Cell Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1093\/stcltm\/szad061","article-title":"Mechanisms of Breast Cancer Stem Cell Specification and Self-Renewal Mediated by Hypoxia-Inducible Factor 1","volume":"12","author":"Semenza","year":"2023","journal-title":"Stem Cells Transl. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e2302584120","DOI":"10.1073\/pnas.2302584120","article-title":"The SHDRA syndrome-associated gene TMEM260 encodes a protein-specific O-mannosyltransferase","volume":"120","author":"Larsen","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"104740","DOI":"10.1016\/j.jbc.2023.104740","article-title":"Nanobody inhibitors of Plexin-B1 identify allostery in plexin-semaphorin interactions and signaling","volume":"299","author":"Cowan","year":"2023","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9636","DOI":"10.1038\/s41467-025-64634-1","article-title":"Proteome atlas for mechanistic discovery and risk prediction of diabetic retinopathy","volume":"16","author":"Yang","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3150","DOI":"10.1016\/j.apsb.2021.03.022","article-title":"3D disorganization and rearrangement of genome provide insights into pathogenesis of NAFLD by integrated Hi-C, Nanopore, and RNA sequencing","volume":"11","author":"Xu","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_27","first-page":"1179","article-title":"Altered expression of the Plexin-B2 system in tuberous sclerosis complex and focal cortical dysplasia IIb lesions","volume":"39","author":"Dai","year":"2024","journal-title":"Histol. Histopathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"102265","DOI":"10.1016\/j.jbc.2022.102265","article-title":"An antagonistic monoclonal anti-Plexin-B1 antibody exerts therapeutic effects in mouse models of postmenopausal osteoporosis and multiple sclerosis","volume":"298","author":"Vogler","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Liu, Z.Z., Liu, L.Y., Zhu, L.Y., Zhu, J., Luo, J.-Y., Wang, Y.-F., and Xu, H.A. (2024). Plexin B3 guides axons to cross the midline in vivo. Front. Cell Neurosci., 18.","DOI":"10.3389\/fncel.2024.1292969"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Halperin, D., Alves, C.J., Lemos, M.R., Dey, S., Tao, H., Kang, S., Li, X., Yue, Z., Li, J., and Dias, R.A. (2025). Cortical tension as a mechanical barrier to safeguard against premature differentiation during neurogenesis. bioRxiv.","DOI":"10.1101\/2025.09.19.677444"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"114627","DOI":"10.1016\/j.intimp.2025.114627","article-title":"Plexin B2 in physiology and pathophysiology of the central nervous system","volume":"155","author":"Wang","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Mao, Y., Evans, E.E., Mishra, V., Balch, L., Eberhardt, A., Zauderer, M., and Gold, W.A. (2021). Anti-Semaphorin 4D Rescues Motor, Cognitive, and Respiratory Phenotypes in a Rett Syndrome Mouse Model. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179465"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.21037\/tp-22-556","article-title":"An X-linked PLXNB3 mutation identified in patients with congenital heart disease with neurodevelopmental disabilities","volume":"11","author":"Feng","year":"2022","journal-title":"Transl. Pediatr."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Wu, C., Rajan, S., Rixen, M., Wohlschlegel, J., and Quinlan, M.E. (2026). The Cappuccino interactome reveals an intracellular role for Semaphorin-2a in Drosophila oogenesis. bioRxiv.","DOI":"10.64898\/2026.05.11.724452"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1038\/s41593-024-01664-w","article-title":"Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer\u2019s disease","volume":"27","author":"Huang","year":"2024","journal-title":"Nat. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7446","DOI":"10.1038\/s41380-021-01236-5","article-title":"Cerebrospinal fluid proteomics targeted for central nervous system processes in bipolar disorder","volume":"26","author":"Isgren","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Huang, H., Shi, C.H., Yang, W., Pi\u00f1a-Crespo, J.C., Bhatnagar, J., Curatolo, J., Murad, R., Shah, P., Campos, A., and Houser, A. (2025). SORLA upregulation suppresses global pathological effects in aged tauopathy mouse brain. bioRxiv.","DOI":"10.1101\/2025.06.25.661599"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6019","DOI":"10.1038\/s41467-021-26296-7","article-title":"Plexin-B2 orchestrates collective stem cell dynamics via actomyosin contractility, cytoskeletal tension and adhesion","volume":"12","author":"Dariolli","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Chapoval, S.P., Lee, M., Lemmer, A., Ajayi, O., Qi, X., Neuwald, A.F., and Keegan, A.D. (2022). Identifying Function Determining Residues in Neuroimmune Semaphorin 4A. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23063024"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"eadw4136","DOI":"10.1126\/sciadv.adw4136","article-title":"Directional guidance to orient Schwann cell alignment in nerve regeneration requires Plexin-B1","volume":"12","author":"Li","year":"2026","journal-title":"Sci. Adv."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"34107","DOI":"10.1021\/acsnano.4c09996","article-title":"Carcinoma-Astrocyte Gap Junction Interruption by a Dual-Targeted Biomimetic Liposomal System to Attenuate Chemoresistance and Treat Brain Metastasis","volume":"18","author":"Cheng","year":"2024","journal-title":"ACS Nano"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e70095","DOI":"10.1002\/jor.70095","article-title":"Ciprofloxacin Treatment in Juvenile Mice Involves Neuronal Activation and Mimics Physical Features of Human Disease","volume":"44","author":"Chittim","year":"2026","journal-title":"J. Orthop. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"ENEURO.0140-26.2026","DOI":"10.1523\/ENEURO.0140-26.2026","article-title":"Coordinated Pre- and Postsynaptic Protein Dynamics Underlie Rapid Sema4D-Induced Inhibitory Synapse Assembly","volume":"13","author":"Pranske","year":"2026","journal-title":"eNeuro"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3743","DOI":"10.1016\/j.neuron.2022.08.016","article-title":"Activation and expansion of presynaptic signaling foci drives presynaptic homeostatic plasticity","volume":"110","author":"Orr","year":"2022","journal-title":"Neuron"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1038\/s41467-021-22603-4","article-title":"Cdk5 and GSK3\u03b2 inhibit fast endophilin-mediated endocytosis","volume":"12","author":"Ferreira","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e2400648121","DOI":"10.1073\/pnas.2400648121","article-title":"Astrocyte-to-microglia communication via Sema4B-Plexin-B2 modulates injury-induced reactivity of microglia","volume":"121","author":"Casden","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Xuan, F.L., Yan, L., Li, Y., Fan, F., Deng, H., Gou, M., Chithanathan, K., Heinla, I., Yuan, L., and Seppa, K. (2022). Glial receptor PLXNB2 regulates schizophrenia-related stress perception via the amygdala. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1005067"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1038\/s41380-019-0491-4","article-title":"The impact of Semaphorin 4C\/Plexin-B2 signaling on fear memory via remodeling of neuronal and synaptic morphology","volume":"26","author":"Simonetti","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5891","DOI":"10.1007\/s12035-022-02948-7","article-title":"Muscone Can Improve Spinal Cord Injury by Activating the Angiogenin\/Plexin-B2 Axis","volume":"59","author":"Zhou","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.mcn.2010.11.005","article-title":"Corrigendum to Semaphorin 4C and 4G are ligands of Plexin-B2 required in cerebellar development","volume":"46","author":"Maier","year":"2011","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e60554","DOI":"10.7554\/eLife.60554","article-title":"Plexin-B2 controls the timing of differentiation and the motility of cerebellar granule neurons","volume":"10","author":"Zagar","year":"2021","journal-title":"eLife"},{"key":"ref_52","first-page":"e64462","article-title":"Modeling Human Cerebellar Development In Vitro in 2D Structure","volume":"187","author":"Madencioglu","year":"2022","journal-title":"J. Vis. Exp."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e70315","DOI":"10.1002\/jcsm.70315","article-title":"Sema4A Protects Against Muscle Atrophy and Promotes Repair by Regulating Intracellular Metabolic Signalling","volume":"17","author":"Wang","year":"2026","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e0799252026","DOI":"10.1523\/JNEUROSCI.0799-25.2026","article-title":"Extracellular HSPA5\/Grp78\/BiP, Acting through Its Receptor Plexin-B3 and Nkx2.8, Regulates Oligodendrocyte Myelination in Mice","volume":"46","author":"Miyamoto","year":"2026","journal-title":"J. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"548","DOI":"10.3390\/pathophysiology30040040","article-title":"RhoG-Binding Domain of Elmo1 Ameliorates Excessive Process Elongation Induced by Autism Spectrum Disorder-Associated Sema5A","volume":"30","author":"Okabe","year":"2023","journal-title":"Pathophysiology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/s41586-024-07715-3","article-title":"In vivo interaction screening reveals liver-derived constraints to metastasis","volume":"632","author":"Borrelli","year":"2024","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"102546","DOI":"10.1016\/j.redox.2022.102546","article-title":"HDLBP-stabilized lncFAL inhibits ferroptosis vulnerability by diminishing Trim69-dependent FSP1 degradation in hepatocellular carcinoma","volume":"58","author":"Yuan","year":"2022","journal-title":"Redox Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1158\/2767-9764.CRC-22-0480","article-title":"Plexin-B1 Mutation Drives Metastasis in Prostate Cancer Mouse Models","volume":"3","author":"Shorning","year":"2023","journal-title":"Cancer Res. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Saxena, S., Prajapati, D.R., Goel, P., Tomar, B., Hayashi, Y., Atri, P., Rachagani, S., Grandgenett, P.M., Hollingsworth, M.A., and Batra, S.K. (2021). Plexin-B3 Regulates Cellular Motility, Invasiveness, and Metastasis in Pancreatic Cancer. Cancers, 13.","DOI":"10.3390\/cancers13040818"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"9646909","DOI":"10.1155\/2022\/9646909","article-title":"Plexin-B2 and Semaphorins Do Not Drive Rhabdomyosarcoma Proliferation or Migration","volume":"2022","author":"Karki","year":"2022","journal-title":"Sarcoma"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1158\/2326-6066.CIR-23-0289","article-title":"PlexinB1 Inactivation Reprograms Immune Cells in the Tumor Microenvironment, Inhibiting Breast Cancer Growth and Metastatic Dissemination","volume":"12","author":"Franzolin","year":"2024","journal-title":"Cancer Immunol. Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Bhasin, S., Dusek, C., Peacock, J.W., Cherkasov, A., Wang, Y., Gleave, M., and Ong, C.J. (2023). Dependency of Tamoxifen Sensitive and Resistant ER+ Breast Cancer Cells on Semaphorin 3C (SEMA3C) for Growth. Cells, 12.","DOI":"10.3390\/cells12131715"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Garg, R., and Williamson, M. (2024). The metastasis-promoting P1597L mutation in PlexinB1 enhances Ras activity. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-12762-0"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1038\/s41417-023-00655-6","article-title":"B-type Plexins promote the GTPase activity of Ran to affect androgen receptor nuclear translocation in prostate cancer","volume":"30","author":"Garg","year":"2023","journal-title":"Cancer Gene Ther."},{"key":"ref_65","first-page":"577","article-title":"Sema4D\/Plexin-B1 promotes the progression of osteosarcoma cells by activating Pyk2-PI3K-AKT pathway","volume":"21","author":"Li","year":"2021","journal-title":"J. Musculoskelet. Neuronal Interact."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.3724\/abbs.2025208","article-title":"Long noncoding RNA HNF1A-AS1 promotes ovarian cancer growth and M2 macrophage polarization by counteracting miR-214-mediated suppression of semaphorin 4D signaling","volume":"58","author":"Liu","year":"2025","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e15172","DOI":"10.7717\/peerj.15172","article-title":"Sema4D silencing increases the sensitivity of nivolumab to B16-F10 resistant melanoma via inhibiting the PI3K\/AKT signaling pathway","volume":"11","author":"Zhang","year":"2023","journal-title":"PeerJ"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e30938","DOI":"10.1002\/pbc.30938","article-title":"A phase 1\/2 study of pepinemab in children, adolescents, or young adults with recurrent or refractory solid tumors: A children\u2019s oncology group consortium report (ADVL1614)","volume":"71","author":"Greengard","year":"2024","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/s41416-022-01814-6","article-title":"Angiogenin and plexin-B2 axis promotes glioblastoma progression by enhancing invasion, vascular association, proliferation and survival","volume":"127","author":"Yang","year":"2022","journal-title":"Br. J. Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/s42003-021-01667-4","article-title":"Plexin-B2 facilitates glioblastoma infiltration by modulating cell biomechanics","volume":"4","author":"Huang","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/s41467-024-55056-6","article-title":"Invasion of glioma cells through confined space requires membrane tension regulation and mechano-electrical coupling via Plexin-B2","volume":"16","author":"Hannah","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"7649","DOI":"10.1038\/s41467-025-62862-z","article-title":"Computational ranking identifies Plexin-B2 in circulating tumor cell clustering with monocytes in breast cancer metastasis","volume":"16","author":"Schuster","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Liang, Y., Meng, K., and Qiu, R. (2021). Circular RNA Circ_0013958 Functions as a Tumor Promoter in Ovarian Cancer by Regulating miR-637\/PLXNB2 Axis. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.644451"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"8445","DOI":"10.1007\/s11033-023-08721-w","article-title":"Expression analysis, clinical significance and potential function of PLXNB2 in acute myeloid leukaemia","volume":"50","author":"Guo","year":"2023","journal-title":"Mol. Biol. Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2220522","DOI":"10.1080\/16078454.2023.2220522","article-title":"CircPLXNB2 regulates acute myeloid leukemia progression through miR-654-3p\/CCND1 axis","volume":"28","author":"Wang","year":"2023","journal-title":"Hematology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1021\/acs.jproteome.2c00332","article-title":"Glycoproteomics Identifies Plexin-B3 as a Targetable Cell Surface Protein Required for the Growth and Invasion of Triple-Negative Breast Cancer Cells","volume":"21","author":"Kuhlmann","year":"2022","journal-title":"J. Proteome Res."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Chapoval, S.P., Gao, H., Fanaroff, R., and Keegan, A.D. (2024). Plexin B1 controls Treg numbers, limits allergic airway inflammation, and regulates mucins. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1297354"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e22924","DOI":"10.1016\/j.heliyon.2023.e22924","article-title":"Comparison of the efficacy of combined budesonide and fexofenadine versus combined fluticasone propionate and fexofenadine on the expression of class-4 semaphorins and their receptors in the peripheral blood cells of patients with allergic rhinitis","volume":"10","author":"Asadi","year":"2023","journal-title":"Heliyon"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1007\/s00403-024-02880-x","article-title":"Plexin B2 tissue expression and related gene polymorphisms in psoriasis and their relation to NB-UVB and Acitretin therapy","volume":"316","author":"Hegazy","year":"2024","journal-title":"Arch. Dermatol. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1093\/bjd\/ljae205","article-title":"Fibroblasts with high matrix metalloproteinase 2 expression regulate CD8+ T-cell residency and inflammation via CD100 in psoriasis","volume":"191","author":"Dong","year":"2024","journal-title":"Br. J. Dermatol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1111\/cod.14414","article-title":"CD100 boosts the inflammatory response in the challenge phase of allergic contact dermatitis in mice","volume":"89","author":"Mraz","year":"2023","journal-title":"Contact Dermat."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Fonseca-Camarillo, G., Furuzawa-Carballeda, J., Aguilar-Le\u00f3n, D., Mart\u00ednez-Ben\u00edtez, B., Barreto-Z\u00fa\u00f1iga, R., and Yamamoto-Furusho, J.K. (2024). Participation of Semaphorin Family and Plexins in the Clinical Course of Patients with Inflammatory Bowel Disease. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252212442"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e70224","DOI":"10.1111\/pai.70224","article-title":"Dibutyl phthalate induces atopic dermatitis via semaphorin\u2013plexin signaling and IL-5, ECHO-COCOA study","volume":"36","author":"Kang","year":"2025","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1016\/j.str.2022.07.008","article-title":"De novo Fc-based receptor dimerizers differentially modulate PlexinB1 function","volume":"30","author":"Matoba","year":"2022","journal-title":"Structure"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.cmet.2021.12.003","article-title":"Senescent immune cells release grancalcin to promote skeletal aging","volume":"34","author":"Li","year":"2022","journal-title":"Cell Metab."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s00018-024-05455-1","article-title":"AP-1B regulates interactions of epithelial cells and intraepithelial lymphocytes in the intestine","volume":"81","author":"Matsumoto","year":"2024","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"8850","DOI":"10.1111\/jcmm.16843","article-title":"Increased airway epithelial cell-derived exosomes activate macrophage-mediated allergic inflammation via CD100 shedding","volume":"25","author":"Yu","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1136\/ard-2022-222728","article-title":"Deciphering the role of cDC2s in Sj\u00f6gren\u2019s syndrome: Transcriptomic profile links altered antigen processes with IFN signature and autoimmunity","volume":"82","author":"Lopes","year":"2023","journal-title":"Ann. Rheum. Dis."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e70114","DOI":"10.1111\/cpr.70114","article-title":"Soluble Sema4D From \u03b3\u03b4 T Cells Exerts Osteoblast Inhibition via Plexin-B\/mTOR Signalling Contributing to Pathogenesis of Bisphosphonate-Related Osteonecrosis of the Jaws","volume":"59","author":"Ou","year":"2026","journal-title":"Cell Prolif."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"160","DOI":"10.5483\/BMBRep.2022-0165","article-title":"Inhibition of the Semaphorin 4D-Plexin-B1 axis prevents calcification in vascular smooth muscle cells","volume":"56","author":"Park","year":"2023","journal-title":"BMB Rep."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s13287-025-04149-0","article-title":"Semaphorin-4D signaling in recruiting dental stem cells for vascular stabilization","volume":"16","author":"Zhang","year":"2025","journal-title":"Stem Cell Res. Ther."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Al Turkestani, N., Zhang, Z., and N\u00f6r, J.E. (2023). Semaphorin 4D Induces Vasculogenic Differentiation of Dental Pulp Stem Cells. Dent. J., 11.","DOI":"10.3390\/dj11070160"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1186\/s13048-023-01309-9","article-title":"The long non-coding RNA NEAT1 promotes the progression of human ovarian cancer through targeting miR-214-3p and regulating angiogenesis","volume":"16","author":"Liu","year":"2023","journal-title":"J. Ovarian Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4632","DOI":"10.1039\/D2LC00632D","article-title":"Sema4D-plexin-B1 signaling in recruiting dental stem cells for vascular stabilization on a microfluidic platform","volume":"22","author":"Zhang","year":"2022","journal-title":"Lab Chip"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Shindo, S., Savitri, I.J., Ishii, T., Ikeda, A., Pierrelus, R., Heidari, A., Okubo, K., Nakamura, S., Kandalam, U., and Rawas-Qalaji, M. (2022). Dual-Function Semaphorin 4D Released by Platelets: Suppression of Osteoblastogenesis and Promotion of Osteoclastogenesis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23062938"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1038\/s41467-021-22131-1","article-title":"Osteoclasts protect bone blood vessels against senescence through the angiogenin\/plexin-B2 axis","volume":"12","author":"Liu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e17885","DOI":"10.1002\/advs.202517885","article-title":"NOX2-Driven Oxidative Stress Promotes EndMT and Uncouples Angiogenesis-Osteogenesis at the Bone-Implant Interface in Diabetes","volume":"13","author":"Wu","year":"2026","journal-title":"Adv. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.jare.2025.03.014","article-title":"Discovery and identification of semaphorin 4D as a bioindicator of high fracture incidence in type 2 diabetic mice with glucose control","volume":"79","author":"Liu","year":"2026","journal-title":"J. Adv. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"105365","DOI":"10.1016\/j.archoralbio.2022.105365","article-title":"Inhibition of Semaphorin 4D\/Plexin-B1 signaling inhibits the subchondral bone loss in early-stage osteoarthritis of the temporomandibular joint","volume":"135","author":"Zhang","year":"2022","journal-title":"Arch. Oral Biol."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Ishii, T., Ruiz-Torruella, M., Yamamoto, K., Yamaguchi, T., Heidari, A., Pierrelus, R., Leon, E., Shindo, S., Rawas-Qalaji, M., and Pastore, M.R. (2022). Locally Secreted Semaphorin 4D Is Engaged in Both Pathogenic Bone Resorption and Retarded Bone Regeneration in a Ligature-Induced Mouse Model of Periodontitis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105630"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s12951-022-01267-2","article-title":"Increased BMSC exosomal miR-140-3p alleviates bone degradation and promotes bone restoration by targeting Plxnb1 in diabetic rats","volume":"20","author":"Wang","year":"2022","journal-title":"J. Nanobiotechnol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"42541","DOI":"10.1038\/s41598-025-26073-2","article-title":"Histopathological effects of lactic acid bacteria enriched white soft cheese in testes of albino rats","volume":"15","author":"Elhanbaly","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"10225536221139887","DOI":"10.1177\/10225536221139887","article-title":"MiR-362-5p inhibits cartilage repair in osteoarthritis via targeting plexin B1","volume":"30","author":"Li","year":"2022","journal-title":"J. Orthop. Surg."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e13103","DOI":"10.1111\/jne.13103","article-title":"PLXNB1 mutations in the etiology of idiopathic hypogonadotropic hypogonadism","volume":"34","author":"Welch","year":"2022","journal-title":"J. Neuroendocrinol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3018","DOI":"10.1111\/jgh.70123","article-title":"The Effects of CD100 Stimulation on Primary Human Hepatocytes (PHHs) and Its Implications in HBV-Related Liver Cirrhosis","volume":"40","author":"Fan","year":"2025","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e70019","DOI":"10.1002\/dvg.70019","article-title":"Generation of Plexin-B1 Conditional Knockout Mouse With CRISPR\/Cas9 Technology","volume":"63","author":"Ni","year":"2025","journal-title":"Genesis"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1007\/s00018-020-03571-2","article-title":"Plexin-Bs enhance their GAP activity with a novel activation switch loop generating a cooperative enzyme","volume":"78","author":"Li","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e70196","DOI":"10.1002\/pro.70196","article-title":"Computational model predicts function of Rho-GTPase binding for plexin receptor GAP activity on Rap1b via dynamic allosteric changes","volume":"34","author":"Bhattarai","year":"2025","journal-title":"Protein Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1038\/s41467-021-21513-9","article-title":"Mechanochemical control of epidermal stem cell divisions by B-plexins","volume":"12","author":"Jiang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1136\/jmg-2023-109728","article-title":"Biallelic variants in Plexin B2 (PLXNB2) cause amelogenesis imperfecta, hearing loss and intellectual disability","volume":"61","author":"Smith","year":"2024","journal-title":"J. Med. Genet."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1093\/ndt\/gfaf180","article-title":"Protein profiles and associated biological pathways among different aetiologies of chronic kidney disease: New insights from DAPA-CKD","volume":"41","author":"Beldhuis","year":"2026","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"666","DOI":"10.2337\/db22-0628","article-title":"Plasma Proteomic Risk Markers of Incident Type 2 Diabetes Reflect Physiologically Distinct Components of Glucose-Insulin Homeostasis","volume":"72","author":"Mi","year":"2023","journal-title":"Diabetes"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41413-023-00309-1","article-title":"Age-related secretion of grancalcin by macrophages induces skeletal stem\/progenitor cell senescence during fracture healing","volume":"12","author":"Zou","year":"2024","journal-title":"Bone Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1111\/jre.13358","article-title":"Plexin-B2 Mediates Orthodontic Tension-Induced Osteogenesis via the RhoA\/F-Actin\/YAP Pathway","volume":"60","author":"Li","year":"2025","journal-title":"J. Periodontal Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e70936","DOI":"10.1096\/fj.202501278RR","article-title":"Matrix Stiffening-Induced SLIT3 Activation in Chondrocytes Drives Cartilage Degradation and Angiogenesis in Temporomandibular Joint Osteoarthritis","volume":"39","author":"Chen","year":"2025","journal-title":"FASEB J."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13020-023-00745-5","article-title":"A novel microbial and hepatic biotransformation-integrated network pharmacology strategy explores the therapeutic mechanisms of bioactive herbal products in neurological diseases: The effects of Astragaloside IV on intracerebral hemorrhage as an example","volume":"18","author":"Hu","year":"2023","journal-title":"Chin. Med."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Zhang, H., Zhu, C., Zhou, X., Wang, L., Deng, L., He, B., and Li, J. (2025). Edaravone dexborneol protected neurological function by targeting NRF2\/ARE and NF-\u03baB\/AIM2 pathways in cerebral ischemia\/reperfusion injury. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1581320"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/9\/1523\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T08:31:12Z","timestamp":1789374672000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/9\/1523"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,14]]},"references-count":117,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["life16091523"],"URL":"https:\/\/doi.org\/10.3390\/life16091523","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,14]]}}}