The KITLG Knockout NCI-H1975 Polyclonal Cells product is a CRISPR/Cas9-edited polyclonal cell population derived from the NCI-H1975 human lung adenocarcinoma line, designed to disrupt endogenous KITLG expression. This loss-of-function model preserves a mixed allelic composition, allowing assessment of KITLG-dependent phenotypes in a context that mirrors native cellular heterogeneity. Researchers can utilize this system to dissect the roles of stem cell factor signaling in cancer biology, without artifacts from monoclonal isolation.
The NCI-H1975 host cell line is an epithelial cell model derived from a human non-small cell lung cancer (NSCLC) adenocarcinoma, characterized by an oncogenic EGFR L858R kinase domain mutation. This activating mutation drives constitutive downstream signaling and is a target for tyrosine kinase inhibitor therapies. Widely employed in lung cancer research, NCI-H1975 cells provide a clinically relevant platform for studying EGFR-dependent tumorigenesis and drug resistance mechanisms, now complemented by KITLG gene disruption.
KITLG encodes stem cell factor (SCF), the cognate ligand for the KIT receptor tyrosine kinase. Ligand binding induces KIT dimerization and autophosphorylation, recruiting adaptors GRB2, SHC, and GAB2 to activate downstream PI3K-AKT and RAS-RAF-MEK-ERK pathways. Additionally, KITLG?CKIT signaling engages JAK-STAT and SRC family kinases. Transcriptional regulation of KITLG is modulated by MITF and SOX10, while downstream effectors include AKT, ERK, and STAT3. These cascades govern cell survival, proliferation, and migration in hematopoiesis, melanogenesis, and development.
In NCI-H1975 cells, KITLG knockout enables dissection of paracrine and autocrine SCF-KIT signaling within the lung adenocarcinoma microenvironment. The EGFR L858R mutation drives oncogenic pathways that share downstream nodes??such as PI3K-AKT and ERK??with KIT, making this model ideal for examining convergent signaling and resistance to EGFR inhibitors. Loss of KITLG may alter tumor cell communication and survival cues, providing insight into how the KIT axis contributes to NSCLC progression and therapeutic resilience.
This polyclonal knockout product supports diverse research areas including cancer stem cell biology, mast cell disorders, melanoma, hematopoiesis, and drug resistance studies. Typical assays encompass western blotting for phospho-KIT, RT-qPCR, cell proliferation and migration/invasion assays, apoptosis detection, and phospho-signaling flow cytometry. The population-based format facilitates functional screens and target validation in the SCF-KIT pathway. For further information or technical assistance, please contact Ascent Research.
