The INHBE Knockout NCI-H1299 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the human INHBE gene in the NCI-H1299 cell line. This loss-of-function model is generated via electroporation of Cas9-sgRNA ribonucleoprotein complexes, resulting in a heterogeneous pool of cells with disrupted INHBE alleles. The polyclonal format avoids clonal selection artifacts and is suitable for applications requiring population-level analysis of gene function.
The host cell line NCI-H1299 is a human non-small cell lung carcinoma epithelial line originally derived from a lymph node metastasis of a lung adenocarcinoma. It is a widely used model for studying epithelial-to-mesenchymal transition (EMT), metastasis, and drug sensitivity, largely owing to its robust response to TGF-beta stimulation. These cells retain metastatic features and are frequently employed to explore TGF-beta-mediated signaling pathways in cancer.
INHBE encodes a secreted ligand of the TGF-beta superfamily. It signals through heteromeric complexes of ACVR2A/ACVR2B type II receptors and ACVR1B type I receptor, phosphorylating SMAD2 and SMAD3, which then partner with SMAD4 to modulate transcription. Key downstream targets include gluconeogenic genes G6PC and PCK1 and the coactivator PPARGC1A. INHBE expression is regulated by insulin, glucagon, and factors FOXO1 and HNF4A, linking it to both TGF-beta/SMAD and insulin signaling. Its role in hepatic glucose production and energy homeostasis underlies its involvement in metabolic diseases.
In the context of NCI-H1299 cells, disruption of INHBE is expected to impair TGF-beta-induced SMAD2/3 activation, thereby altering downstream transcriptional responses involved in proliferation, apoptosis, EMT, and metabolic reprogramming. Since TGF-beta signaling can either suppress or promote tumor progression depending on the cellular context, this knockout model enables dissection of the precise role of INHBE in lung adenocarcinoma. It may help clarify how this ligand influences the interplay between tumor metabolism and aggressive cancer phenotypes.
This product is well-suited for a variety of research applications, including western blot and RT-qPCR confirmation of INHBE disruption, phospho-SMAD2/3 analysis, metabolic flux analyses using glucose uptake or Seahorse assays, and RNA-seq transcriptomic profiling. It supports drug target validation in metabolic disease contexts such as type 2 diabetes and non-alcoholic fatty liver disease, as well as cancer metabolism research. For custom inquiries or technical support, please contact Ascent Research.
