Related Experiment Video
Updated: Jul 19, 2026

Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation
Published on: June 27, 2017
Signaling pathways influencing SLF and c-kit-mediated survival and proliferation
1The Arthritis and Immune Disorder Research Centre, University Health Network and the Department of Immunology, University of Toronto, Toronto, Ontario, Canada. Berger@uhnres.utoronto.ca
Abstract:
Steel factor (SLF) and c-Kit are a ligand-receptor pair that regulates growth and activation of a variety of hemopoietic and non-hemopoietic cells. This review describes our work investigating downstream signaling pathways activated by SLF, with particular emphasis on signaling differences associated with soluble vs membrane- bound ligand, and our identification of an important role for PLC activation and Ca2+ influx in supporting c-Kit positive cells in vitro and in vivo. This work led to the identification of a unique form of cell death termed activation enhanced cell death (AECD) that involves stimulating a cell with a growth or activation signal while concurrently blocking Ca2+ influx. Approaches that we have taken toward identifying cellular factors associated with sensitivity and resistance to AECD are summarized, as is our experience with a variety of experimental models. The use of econazole as a calcium channel blocker and its mechanism of action are described, as is its potential for development as an anticancer therapeutic.
Insights
Steel factor (SLF) and c-Kit signaling pathways were investigated. Researchers identified a unique cell death mechanism (AECD) and explored econazole
Area of Science:
- Cellular signaling pathways
- Hematopoiesis
- Cancer biology
Background:
- Steel factor (SLF) and c-Kit form a crucial ligand-receptor pair.
- This pair regulates the growth and activation of hemopoietic and non-hemopoietic cells.
Purpose of the Study:
- Investigate downstream signaling pathways activated by SLF.
- Identify differences in signaling between soluble and membrane-bound SLF.
- Explore the role of PLC activation and calcium influx in supporting c-Kit positive cells.
Main Methods:
- Analysis of SLF downstream signaling pathways.
- Investigation of soluble vs. membrane-bound ligand effects.
- Characterization of calcium (Ca2+) influx mechanisms.
- Identification of factors influencing Activation Enhanced Cell Death (AECD) sensitivity.
- Evaluation of econazole as a calcium channel blocker.
Main Results:
- Discovered distinct signaling pathways for soluble and membrane-bound SLF.
- Identified PLC activation and Ca2+ influx as critical for c-Kit positive cell support.
- Defined Activation Enhanced Cell Death (AECD), a novel cell death pathway.
- Identified factors contributing to AECD sensitivity and resistance.
- Demonstrated econazole's potential as an anticancer therapeutic via calcium channel blockade.
Conclusions:
- SLF-c-Kit signaling is complex, with variations based on ligand form.
- Calcium influx plays a vital role in cell survival and is a target for AECD.
- AECD represents a promising avenue for cancer therapy development.
- Econazole shows potential as an anticancer agent by blocking calcium channels.
More Related Videos
07:38Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
Published on: June 6, 2025
09:18Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Related Concept Videos
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
MAPK Signaling Cascades
Amplifying Signals via Enzymatic Cascade
PI3K/mTOR/AKT Signaling Pathway
The JAK-STAT Signaling Pathway
mTOR Signaling and Cancer Progression
The mTOR pathway or the...