The GPR75 Knockout PaTu 8988t Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the GPR75 gene in the human pancreatic adenocarcinoma cell line PaTu 8988t. This polyclonal product has undergone CRISPR/Cas9-mediated gene disruption, generating a heterogeneous pool of cells with targeted loss of GPR75 function.
The PaTu 8988t cell line is derived from a human metastatic pancreatic adenocarcinoma and exhibits an aggressive phenotype driven by a KRAS G12V mutation and TP53 mutant status. This genetic context is characteristic of pancreatic ductal adenocarcinoma and provides a clinically relevant platform for studying oncogenic signaling and metabolic dependencies in cancer. The metastatic nature of the parental cells further allows for the investigation of tumor cell motility, invasion, and metastatic potential in the context of GPR75 knockout.
GPR75 is an orphan G protein-coupled receptor (GPCR) that couples to G??s, activating adenylyl cyclase (ADCY) and elevating intracellular cAMP, which then stimulates protein kinase A (PKA) and phosphorylates the transcription factor CREB. Concurrently, GPR75 signaling activates the MAPK/ERK pathway, leading to ERK1/2 phosphorylation. Receptor activity is modulated by G protein-coupled receptor kinases (GRKs) and ??-arrestins, with direct interaction with ??-arrestin-2 facilitating desensitization and internalization. This signaling network governs energy homeostasis and insulin secretion, with downstream effects on CREB and ERK1/2 transcriptional responses. Disruption of GPR75 by CRISPR/Cas9 thus interrupts this signaling axis, impairing cAMP-PKA and ERK1/2 pathway output.
In the PaTu 8988t background, GPR75 knockout provides a unique model to dissect the intersection between orphan GPCR signaling and the KRAS/TP53-driven pancreatic cancer phenotype. The disruption of GPR75-mediated cAMP-PKA and ERK1/2 pathways may influence cell proliferation, metabolic reprogramming, and insulin secretion-related responses, potentially altering the tumorigenic properties of these metastatic cells. Given the emerging evidence linking GPR75 to metabolic disorders such as obesity and type 2 diabetes, this knockout model enables the exploration of how GPR75-associated energy homeostasis pathways interface with cancer cell metabolism and survival. The polyclonal format preserves population heterogeneity, enabling bulk functional studies without clonal selection bias.
Researchers can employ the GPR75 Knockout PaTu 8988t Polyclonal Cells in a variety of downstream assays, including Western blot analysis for phospho-CREB and phospho-ERK1/2 to monitor signaling pathway activity, cAMP ELISA to quantify second messenger levels, and RT-qPCR to assess transcriptional changes in downstream targets. Functional studies such as cell proliferation, migration/invasion, and metabolic assays can evaluate the impact of GPR75 loss on cancer cell behavior, while drug sensitivity studies enable target validation for metabolic disease or oncology therapeutics. This product is also well-suited for deorphanization screening assays to identify putative GPR75 ligands and for investigating metabolic signaling in pancreatic adenocarcinoma. For further technical information, please contact Ascent Research.
