Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Aug 11:12:932608.
doi: 10.3389/fonc.2022.932608. eCollection 2022.

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

Sungjin David Park  1 , Apryl S Saunders  1 , Megan A Reidy  1 , Dawn E Bender  1 , Shari Clifton  2 , Katherine T Morris  1
Affiliations
Review

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

Sungjin David Park et al. Front Oncol. .

Abstract

Granulocyte colony-stimulating factor receptor (GCSFR) is a critical regulator of granulopoiesis. Studies have shown significant upregulation of GCSFR in a variety of cancers and cell types and have recognized GCSFR as a cytokine receptor capable of influencing both myeloid and non-myeloid immune cells, supporting pro-tumoral actions. This systematic review aims to summarize the available literature examining the mechanisms that control GCSFR signaling, regulation, and surface expression with emphasis on how these mechanisms may be dysregulated in cancer. Experiments with different cancer cell lines from breast cancer, bladder cancer, glioma, and neuroblastoma are used to review the biological function and underlying mechanisms of increased GCSFR expression with emphasis on actions related to tumor proliferation, migration, and metastasis, primarily acting through the JAK/STAT pathway. Evidence is also presented that demonstrates a differential physiological response to aberrant GCSFR signal transduction in different organs. The lifecycle of the receptor is also reviewed to support future work defining how this signaling axis becomes dysregulated in malignancies.

Keywords: CSF3R; GCSFR; cancer; regulation; signaling/signaling pathways.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Overall GCSFR Structure.
Figure 2
Figure 2
General Overview of GCSFR Signal Pathways. Adapted from “Hippo Pathway in Mammals”, by BioRender.com (2022). Retrieved from https://app.biorender.com/biorender-templates.
Figure 3
Figure 3
STAT3 Activation Mechanisms. Adapted from “Cytokine Signaling through the JAK-STAT Pathway”, by BioRender.com (2022). Retrieved from https://app.biorender.com/biorender-templates.
Figure 4
Figure 4
SOCS Inhibition Mechanisms. Adapted from “Cytokine Receptor Families”, by BioRender.com (2022). Retrieved from https://app.biorender.com/biorender-templates.
Figure 5
Figure 5
Transcription Factors of GCSFR (CSF3R). Adapted from “CREB Signaling Pathway”, by BioRender.com (2022). Retrieved from https://app.biorender.com/biorender-templates.
Figure 6
Figure 6
GCSFR Degradation and Recycle Mechanisms. Adapted from “Endocytosis and Exocytosis with Membrane Rupture (Layout)”, by BioRender.com (2022). Retrieved from https://app.biorender.com/biorender-templates.
See this image and copyright information in PMC

References

    1. Azoulay E, Delclaux C. Is there a place for granulocyte colony-stimulating factor in non-neutropenic critically ill patients? Intensive Care Med (2004) 30:10–7. doi: 10.1007/s00134-003-2049-8 - DOI - PMC - PubMed
    1. Bennett CL, Djulbegovic B, Norris LB, Armitage JO. Colony-stimulating factors for febrile neutropenia during cancer therapy. N. Engl J Med (2013) 368:1131–9. doi: 10.1056/NEJMct1210890 - DOI - PMC - PubMed
    1. Agarwal S, Lakoma A, Chen Z, Hicks J, Metelitsa LS, Kim ES, et al. . G-CSF promotes neuroblastoma tumorigenicity and metastasis via STAT3-dependent cancer stem cell activation. Cancer Res (2015) 75:2566–79. doi: 10.1158/0008-5472.CAN-14-2946 - DOI - PMC - PubMed
    1. Wang L, Arcasoy MO, Watowich SS, Forget BG. Cytokine signals through STAT3 promote expression of granulocyte secondary granule proteins in 32D cells. Exp Hematol (2005) 33:308–17. doi: 10.1016/j.exphem.2004.11.014 - DOI - PMC - PubMed
    1. Wojtukiewicz MZ, Sierko E, Skalij P, Kaminska M, Zimnoch L, Brekken RA, et al. . Granulocyte-colony stimulating factor receptor, tissue factor, and VEGF-r bound VEGF in human breast cancer in loco. Adv Clin Exp Med (2016) 25:505–11. doi: 10.17219/acem/62398 - DOI - PubMed

LinkOut - more resources