The SCF/KIT signaling pathway in multisystem diseases: Mechanisms and therapeutic targeting
- 1Department of Nephrology and Rheumatology, Zhaotong Hospital of Traditional Chinese Medicine, Zhaotong, Yunnan, China.
- 2School of Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei, China
- 3Department of Geriatrics, Hubei Provincial Hospital of Traditional Chinese Medicine, Hubei, Wuhan, China
Abstract
The stem cell factor (SCF)/KIT signaling axis regulates the survival, proliferation, differentiation, and migration of hematopoietic stem and progenitor cells, mast cells, interstitial cells of Cajal, germ cells, and melanocytes through multiple downstream pathways, including PI3K/AKT and RAS/MAPK. Its biological and pathological effects are determined by cell lineage, ligand presentation, and mutational context. At the pathway level, SCF expression and processing, KIT abundance, and activating mutations determine signal initiation and intensity, whereas CBL-mediated receptor degradation and SHP-1-mediated dephosphorylation limit signal duration. This narrative review critically examines representative multisystem diseases for which SCF/KIT involvement is supported by genetic, functional, or therapeutic evidence and distinguishes established treatments from investigational approaches. Activating KIT mutations drive gastrointestinal stromal tumors (GISTs) and systemic mastocytosis. Clinically established KIT-directed tyrosine kinase inhibitors, including imatinib for mutation-sensitive GIST and midostaurin or avapritinib for advanced systemic mastocytosis, have transformed disease management. By contrast, increased local SCF availability and KIT-dependent mast cell persistence may amplify inflammatory diseases, whereas impaired signaling is associated with gastrointestinal dysmotility, reproductive dysfunction, and pigmentary abnormalities. Emerging anti-KIT antibodies are being investigated as a strategy to deplete mast cells in chronic urticaria, whereas recombinant SCF-based mobilization has largely historical clinical relevance and regenerative applications remain experimental. Mutation-dependent drug sensitivity, polyclonal secondary resistance, multikinase-related toxicity, and on-target effects in normal KIT-dependent tissues remain major challenges. A disease-, genotype-, and cell-specific framework is therefore essential for translating SCF/KIT biology into safe and effective precision therapies.
Related
- Environmental enrichment as a multisystem modulator of neurotransmitter function: mechanisms, plasticity, and therapeutic implications
- Neutrophil Extracellular Traps at the Asthma + COPD Interface: Mechanisms, Experimental Models, and Therapeutic Targeting
- Special Issue “Molecular Mechanisms and Therapeutic Targeting of Inflammatory Complications”
- Stem cell factor in allergic diseases: mechanisms of type 2 immunity and therapeutic opportunities
- Fibrotic Remodeling in Retinal Vascular Diseases: Cellular Origins, Molecular Mechanisms, and Therapeutic Perspectives.
BibTeX
@article{ma2026scfkit,
title = {{The SCF/KIT signaling pathway in multisystem diseases: Mechanisms and therapeutic targeting}},
author = {Ruidie Ma and Xueliang Wang and Yingbing Mei},
journal = {Science Progress},
year = {2026},
month = sep,
doi = {10.1177/00368504261492893},
url = {https://doi.org/10.1177/00368504261492893},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - The SCF/KIT signaling pathway in multisystem diseases: Mechanisms and therapeutic targeting
AU - Ruidie Ma
AU - Xueliang Wang
AU - Yingbing Mei
PY - 2026
DA - 2026/09/29
JO - Science Progress
DO - 10.1177/00368504261492893
UR - https://doi.org/10.1177/00368504261492893
AB - The stem cell factor (SCF)/KIT signaling axis regulates the survival, proliferation, differentiation, and migration of hematopoietic stem and progenitor cells, mast cells, interstitial cells of Cajal, germ cells, and melanocytes through multiple downstream pathways, including PI3K/AKT and RAS/MAPK. Its biological and pathological effects are determined by cell lineage, ligand presentation, and mutational context. At the pathway level, SCF expression and processing, KIT abundance, and activating mutations determine signal initiation and intensity, whereas CBL-mediated receptor degradation and SHP-1-mediated dephosphorylation limit signal duration. This narrative review critically examines representative multisystem diseases for which SCF/KIT involvement is supported by genetic, functional, or therapeutic evidence and distinguishes established treatments from investigational approaches. Activating KIT mutations drive gastrointestinal stromal tumors (GISTs) and systemic mastocytosis. Clinically established KIT-directed tyrosine kinase inhibitors, including imatinib for mutation-sensitive GIST and midostaurin or avapritinib for advanced systemic mastocytosis, have transformed disease management. By contrast, increased local SCF availability and KIT-dependent mast cell persistence may amplify inflammatory diseases, whereas impaired signaling is associated with gastrointestinal dysmotility, reproductive dysfunction, and pigmentary abnormalities. Emerging anti-KIT antibodies are being investigated as a strategy to deplete mast cells in chronic urticaria, whereas recombinant SCF-based mobilization has largely historical clinical relevance and regenerative applications remain experimental. Mutation-dependent drug sensitivity, polyclonal secondary resistance, multikinase-related toxicity, and on-target effects in normal KIT-dependent tissues remain major challenges. A disease-, genotype-, and cell-specific framework is therefore essential for translating SCF/KIT biology into safe and effective precision therapies.
SN - 0036-8504
SN - 2047-7163
ER -