GPR75 Knockout SK-OV-3 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population designed for investigating the orphan G protein-coupled receptor GPR75 in a human ovarian adenocarcinoma background. This product consists of a heterogeneous pool of SK-OV-3 cells carrying CRISPR/Cas9-mediated gene disruption at the GPR75 locus, enabling loss-of-function studies without clonal selection. The polyclonal format preserves genetic diversity, reducing clonal artifacts while providing a robust model to examine GPR75-dependent signaling and cellular phenotypes.
The host cell line, SK-OV-3, is derived from the ascites of a patient with ovarian adenocarcinoma and is widely used as a model for high-grade serous ovarian carcinoma. These cells exhibit epithelial morphology and harbor a TP53 mutation, recapitulating key features of advanced ovarian cancer, including chemoresistance and metastatic potential. The well-characterized genetic and phenotypic traits of SK-OV-3 make it an ideal platform for exploring the intersection of oncogenic processes and metabolic regulation.
At the molecular level, GPR75 is an orphan receptor that signals primarily via the Gs protein?Cadenylate cyclase (ADCY)?CcAMP?CPKA axis, with downstream activation of CREB and ERK1/2 cascades. The receptor also engages ??-arrestin-mediated pathways and is implicated in modulating insulin secretion and hypothalamic appetite control. By disrupting GPR75 expression, these polyclonal knockout cells abolish receptor-mediated cAMP production, thereby enabling precise dissection of the GPR75?CGs?CADCY?CcAMP?CPKA?CCREB signaling module and its crosstalk with MAPK/ERK effectors.
In the SK-OV-3 ovarian cancer context, GPR75 knockout provides a physiologically relevant system to evaluate the receptor??s contributions to tumor cell proliferation, metabolic reprogramming, and resistance to chemotherapy. Given SK-OV-3??s established use in chemoresistance and metastasis research, this knockout model allows investigators to interrogate whether GPR75-driven signaling influences cancer cell survival under nutrient stress or drug exposure, linking metabolic sensing to malignant phenotypes.
Typical applications include cAMP accumulation assays to quantify functional knockout, western blot analysis of phosphorylated CREB and ERK1/2 to map downstream signaling, and MTT or colony formation assays to assess cell viability and proliferative capacity. Metabolic flux analysis via Seahorse and RT-qPCR profiling of GPR75-regulated transcripts further support studies in cancer metabolism and therapeutic target validation. For further information, please contact Ascent Research.
