A review of granulocyte colony-stimulating factor receptor signaling and regulation with implications for cancer

Park, Sungjin David; Saunders, Apryl S.; Reidy, Megan A.; Bender, Dawn E.; Clifton, Shari; Morris, Katherine T.

doi:10.3389/fonc.2022.932608

Cited by 11 publications

(9 citation statements)

References 108 publications

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“…GCSF actions are mediated by activation of its receptor, named GCSFR or CD114. Recombinant human GCSF is clinically used to prevent neutropenia, due to its effects on neutrophil mobilization and maturation [ 32 ]. GCSF/CD114 signaling has also been investigated as a modulator of neuronal survival, synaptic plasticity [ 6 , 28 , 29 , 30 , 31 ], and cancer [ 7 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

Gene Expression of CSF3R/CD114 Is Associated with Poorer Patient Survival in Glioma

Bark,

Dalmolin,

Malafaia

et al. 2024

IJMS

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Gliomas comprise most cases of central nervous system (CNS) tumors. Gliomas afflict both adults and children, and glioblastoma (GBM) in adults represents the clinically most important type of malignant brain cancer, with a very poor prognosis. The cell surface glycoprotein CD114, which is encoded by the CSF3R gene, acts as the receptor for the granulocyte colony stimulating factor (GCSF), and is thus also called GCSFR or CSFR. CD114 is a marker of cancer stem cells (CSCs), and its expression has been reported in several cancer types. In addition, CD114 may represent one among various cases where brain tumors hijack molecular mechanisms involved in neuronal survival and synaptic plasticity. Here, we describe CSF3R mRNA expression in human gliomas and their association with patient prognosis as assessed by overall survival (OS). We found that the levels of CSF3R/CD114 transcripts are higher in a few different types of gliomas, namely astrocytoma, pilocytic astrocytoma, and GBM, in comparison to non-tumoral neural tissue. We also observed that higher expression of CSF3R/CD114 in gliomas is associated with poorer outcome as measured by a shorter OS. Our findings provide early evidence suggesting that CSF3R/CD114 shows a potential role as a prognosis marker of OS in patients with GBM.

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Section: Discussionmentioning

confidence: 99%

Gene Expression of CSF3R/CD114 Is Associated with Poorer Patient Survival in Glioma

Bark,

Dalmolin,

Malafaia

et al. 2024

IJMS

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“…The main function of G-CSF is to induce proliferation, migration and myeloid differentiation of hematopoietic stem cells. However, G-CSF can also protect from cell death and have immunomodulatory activity [31, 56, 79, 80]. For instance, rhG-CSF’s widest use is to treat neutropenia acquired as a result of cytotoxic anti-cancer therapy [32].…”

Section: Discussionmentioning

confidence: 99%

“…To pinpoint biased G-CSFR signaling by designed agonists at the level of downstream signal propagation, we quantified the phosphorylation of STAT3 and STAT5 proteins in NFS-60 cells treated with rhG-CSF or designed agonists. Since STAT3 phosphorylation occurs at the membranedistal regions of the intracellular segments of the receptor , while STAT5 is phosphorylated at the membrane-proximal receptor region [56], we reasoned that the relative ratio of pSTAT3/5 might be altered by different design agonists. We therefore aimed to investigate whether design proteins can affect STATs phosphorylation dependent on the engagement geometry of two G-CSFR receptor subunits.…”

Section: Different Design Agonists Tune G-csfr Signaling Amplitudes K...mentioning

confidence: 99%

Tuning of granulopoietic signaling byde novodesigned agonists

Ullrich,

Pollmann,

Ritter

et al. 2023

Preprint

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Enhancing cytokine-based therapies by systematically tuning how an agonist associates its receptor is emerging as a powerful new concept in drug discovery. Here, we report the design and characterization of agonists that tune the granulocyte-colony stimulating factor receptor (G-CSFR) activity, which is central for the proliferation and granulocytic differentiation of hematopoietic stem cells. Using design agonists, we study the impact of varying the receptor-binding affinity and dimerization geometry on receptor association, downstream signaling, and cellular response. Hence, we achieved agonists with altered signaling specificities that are hyper-thermostable, can outcompete the native ligand (G-CSF), and bias granulopoietic differentiation over triggering proliferation. Furthermore, the design agonists differentially modulate the kinetics and amplitudes of signal transduction pathways, and gene expression patterns. Unlike G-CSF, they achieve selective activation of hematopoietic functions with minimal undesired immunomodulatory effects. These findings demonstrate the potential of dissecting the complex G-CSFR signaling, and open ways for new therapeutic applications.Graphical abstract

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“…Low occupancy at the receptors is adequate to achieve the maximum biological response. G-CSFR is composed of a single extracellular domain, a transmembrane domain, and an intracellular domain [62,63]. The extracellular domain contains immunoglobulin (Ig)like domains, a cytokine receptor homologous (CRH) domain, and three fibronectin (FN)-III-like repeats.…”

Section: Neuroprotective Properties Of Granulocyte Colony-stimulating...mentioning

confidence: 99%

Neuroprotective Properties of Peptides

Erbaş¹,

Altuntaş²,

Nesil³

et al. 2023

Rare Neurodegenerative Disorders - New Insights [Working Title]

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The development of a treatment strategy for neurodegenerative disorders is a serious issue for the healthcare world and a crucial subject of discussion. In the past two decades, a lot of focus has been placed on identifying the pathophysiological processes involved in neuronal death linked to neurodegenerative disorders and developing a variety of treatment options for neuroprotection. Numerous research teams have studied the use of peptides as neuroprotective treatments for different types of neurodegenerative disorders for a long time. The review aims to provide details about the roles of erythropoietin (EPO), glucagon-like peptide-1 (GLP-1), granulocyte colony-stimulating factor (G-CSF), and oxytocin (OXT) in neurodegenerative disorders as well as what cellular and molecular mechanisms they trigger to elicit the neuroprotective action, with a focus on neurodegenerative disorders.

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A review of granulocyte colony-stimulating factor receptor signaling and regulation with implications for cancer

Cited by 11 publications

References 108 publications

Gene Expression of CSF3R/CD114 Is Associated with Poorer Patient Survival in Glioma

Gene Expression of CSF3R/CD114 Is Associated with Poorer Patient Survival in Glioma

Tuning of granulopoietic signaling byde novodesigned agonists

Neuroprotective Properties of Peptides

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