The GPR75 Knockout LoVo Polyclonal Cells product provides a polyclonal population of LoVo cells harboring CRISPR/Cas9-mediated disruption of the GPR75 gene. This knockout pool models loss of GPR75 function, enabling studies of its role in signaling and disease. The heterogeneous editing events avoid clonal artifacts, offering a robust system for functional genomics.
The LoVo parental line originates from a metastatic colorectal adenocarcinoma lymph node biopsy of a 56-year-old Caucasian male. These cells exhibit an adherent, glandular epithelial phenotype and are extensively used as a human colon carcinoma model. The metastatic derivation endows LoVo cells with aggressive tumorigenic properties, making them particularly suitable for investigating colorectal cancer progression, invasion, and chemoresistance mechanisms.
GPR75 is an orphan GPCR that preferentially couples to G??s proteins, leading to activation of adenylate cyclase and subsequent intracellular cAMP accumulation. Elevated cAMP stimulates protein kinase A (PKA), which phosphorylates the transcription factor CREB, thereby modulating cAMP response element-dependent gene expression. Concurrently, GPR75 signaling engages the MAPK/ERK pathway, indicated by increased ERK1/2 phosphorylation, and interacts with beta-arrestins that serve as signaling scaffolds. Downstream targets thus include cAMP, PKA, phospho-CREB, and phospho-ERK1/2. Although the endogenous ligand remains unidentified, GPR75 may be regulated by neuropeptides or metabolic cues. Disruption of GPR75 in this polyclonal knockout model silences these signaling cascades, providing a clean background to study receptor-dependent molecular events.
Within the colorectal adenocarcinoma context, GPR75 has been implicated in cell proliferation and survival. The LoVo polyclonal knockout cells offer a clinically relevant platform to examine how loss of GPR75 impacts malignant phenotypes such as anchorage-independent growth, migration, and invasion. Because LoVo cells are metastatic in origin, this model may reveal GPR75??s role in advanced-stage colon cancer. Additionally, the signaling link to cAMP and MAPK pathways makes it a powerful system to explore crosstalk between metabolic sensing and oncogenic signaling, as GPR75 is also tied to appetite regulation and energy homeostasis. Thus, the knockout cells facilitate validation of GPR75 as a therapeutic target in colorectal cancer and metabolic disorders.
This polyclonal knockout model supports a broad range of experimental workflows. For signaling analysis, researchers can employ intracellular cAMP measurement assays, western blotting for phospho-CREB and phospho-ERK1/2, and RT-qPCR for downstream transcriptional targets. Functional readouts such as cell proliferation, colony formation, and transwell migration/invasion assays delineate the receptor??s role in tumorigenicity. Drug sensitivity profiling via MTT assays and apoptosis detection by flow cytometry can uncover GPR75-dependent chemoresistance mechanisms. In obesity and neuropsychiatric research, the cells serve as an in vitro system to investigate neuropeptide-modulated GPCR actions. For further technical specifications or ordering information, please contact Ascent Research.
