The INHBE Knockout PaTu 8988t Polyclonal Cells product provides a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human pancreatic ductal adenocarcinoma cell line PaTu 8988t, featuring targeted disruption of the INHBE gene. This polyclonal population consists of a heterogeneous mixture of edited alleles generated by CRISPR/Cas9-mediated gene editing, ensuring a broad representation of loss-of-function variants without clonal selection. The cells are supplied as a pooled population, enabling immediate use in functional studies that require a knockout background while maintaining the biological variability inherent to polyclonal populations, making them suitable for high-throughput screening and pooled genetic analyses.
PaTu 8988t is an established human pancreatic adenocarcinoma cell line harboring a KRAS G12V driver mutation, exhibiting an epithelial morphology and robust tumorigenicity in immunocompromised mouse models. This cell line serves as a critical model for KRAS-driven pancreatic cancer, widely employed to investigate tumor growth, invasion, metastasis, and mechanisms of drug resistance. Its genetic background and tumorigenic properties make it particularly relevant for dissecting oncogenic signaling networks and evaluating therapeutic interventions in a clinically relevant context of pancreatic cancer.
INHBE encodes the inhibin beta E subunit, a member of the TGF-beta superfamily that forms activin E homodimers or heterodimers with other beta subunits, such as INHBA. These secreted ligands bind to activin type II receptors (ACVR2A/ACVR2B) and type I receptor ACVR1B, leading to phosphorylation and activation of downstream effectors SMAD2 and SMAD3, which then complex with SMAD4 to regulate transcription of target genes including ID1 and CTGF. Upstream, INHBE expression is transcriptionally regulated by FOXO1 and modulated by hormonal cues such as insulin, glucagon, and glucocorticoids. The encoded protein functions as a hepatokine involved in systemic insulin sensitivity and energy homeostasis, linking hepatic signaling to metabolic control, while also playing a context-dependent role in cell growth and differentiation through activin/inhibin pathway dynamics.
In the PaTu 8988t pancreatic cancer model, disruption of INHBE provides a powerful tool to examine the intersection of TGF-beta signaling, metabolic reprogramming, and oncogenic KRAS-driven malignancy. Loss of INHBE function allows researchers to interrogate how activin E-mediated signaling influences tumor cell proliferation, survival, and metabolic adaptation, as well as its potential role in shaping the tumor microenvironment. This model is particularly valuable given the emerging links between systemic metabolic regulators and pancreatic cancer progression, offering insight into whether INHBE acts as a tumor-cell-intrinsic modulator or via paracrine effects within the tumor stroma.
This polyclonal knockout product is suitable for a range of research applications including investigation of INHBE-dependent metabolic changes using glucose uptake assays and Seahorse metabolic flux analysis, analysis of TGF-beta/SMAD pathway alterations via phospho-SMAD2/3 western blotting and RT-qPCR, and functional studies via migration/invasion assays and xenograft tumor growth models. It can be employed in high-throughput screens for anti-obesity or diabetes therapeutics targeting the hepatokine axis, as well as in CRISPR-Cas9 knockout validation and co-immunoprecipitation experiments to map protein interactions. For further inquiries regarding product availability, custom modifications, or technical support, please contact Ascent Research.
