Description

The GDF15 Knockout MDA-MB-231 Cell Line is a CRISPR/Cas9-edited knockout cell line in which the GDF15 gene encoding growth differentiation factor 15 has been disrupted. This stable loss-of-function model is derived from the MDA-MB-231 parental line, ensuring isogenic experimental controls for studying GDF15-dependent processes.

MDA-MB-231 is a human epithelial cell line isolated from the pleural effusion of a metastatic breast adenocarcinoma patient. It displays a triple-negative phenotype, lacking ER, PR, and HER2 expression, and is characterized by high invasiveness and tumorigenicity. This line serves as a standard model for aggressive, mesenchymal-like triple-negative breast cancer (TNBC) and is extensively used to investigate metastatic progression and drug resistance.

GDF15 is a stress-responsive member of the TGF-?? superfamily that functions as a secreted cytokine. Its transcription is upregulated by diverse stressors, with key transcription factors such as p53, NF-??B, EGR1, ATF4, and CHOP mediating induction, often in concert with inflammatory signals like IL-1?? and TNF-??. Secreted GDF15 specifically binds to the GFRAL receptor, which then recruits the RET co-receptor to initiate intracellular signaling. This ligand?Creceptor complex activates the RAS-RAF-MEK-ERK kinase cascade and the PI3K-AKT pathway, and also modulates SMAD2/3 and NF-??B activity. Consequently, GDF15 exerts control over cellular apoptosis, metabolic adaptation, and inflammatory responses.

Disruption of GDF15 in the MDA-MB-231 background ablates GDF15-GFRAL-RET-dependent signaling, yielding a precise loss-of-function tool for TNBC research. Without GDF15, the cells no longer activate downstream MAPK/ERK and PI3K/AKT pathways, enabling clear assignment of phenotypes to GDF15 function. This knockout model is particularly valuable for probing GDF15’s contributions to aggressive features of triple-negative breast cancer, including enhanced proliferation, migratory capacity, invasion, and resistance to chemotherapeutic agents. It also facilitates study of GDF15-driven metabolic changes and its paracrine effects in the tumor microenvironment.

Typical experimental applications include Western blot analysis of phosphorylated ERK and AKT, RT-qPCR profiling of downstream target genes, and cell proliferation assays to quantify GDF15-dependent growth. Transwell migration and invasion assays, coupled with Annexin V apoptosis assays, provide functional readouts of motility and cell death, while RNA-sequencing reveals transcriptome-wide changes. For in vivo analysis, xenograft tumor growth studies allow assessment of GDF15’s role in tumor formation and progression. Additionally, this cell line is well-suited for high-throughput screening of inhibitors or antibodies targeting the GDF15-GFRAL signaling axis. For further information or to discuss customized project needs, please contact Ascent Research.