The DPYSL2 Knockout 786-O Polyclonal Cells are a heterogeneous population of human renal epithelial cells engineered via CRISPR/Cas9-mediated gene disruption to ablate functional expression of DPYSL2 (collapsin response mediator protein 2, CRMP2). This polyclonal knockout product format provides a pooled loss?of?function model in the 786?O cellular background, enabling studies of DPYSL2?dependent processes without the constraints of single?clone selection.
Derived from a clear cell renal cell carcinoma, the 786?O cell line is a widely used tumorigenic model of human kidney epithelial cells. Its well?characterized genetic and phenotypic landscape, including a VHL?null status and constitutive HIF pathway activation, makes it particularly relevant for investigating molecular drivers of renal tumor progression and metastatic dissemination.
DPYSL2 encodes a microtubule?associated protein that serves as a key integrator of cytoskeletal dynamics. In response to Semaphorin?3A (Sema3A) signaling, ligand?bound Nrp1/PlexinA receptors trigger a phosphorylation cascade wherein Cdk5 primes CRMP2 for subsequent phosphorylation by GSK3??. This dual phosphorylation attenuates CRMP2 binding to tubulin heterodimers and promotes its interaction with actin?associated adaptors, including NUMB, thereby orchestrating microtubule destabilization, actin cytoskeleton reorganization, and growth cone collapse. CRMP2 also functions in receptor?mediated endocytosis through NUMB and intersects with Rho GTPase?governed pathways to regulate cell polarity and directed migration.
In the 786?O renal carcinoma context, disruption of DPYSL2 is anticipated to compromise pro?invasive signaling circuits that rely on CRMP2?dependent cytoskeletal restructuring. As CRMP2 phosphorylation has been implicated in cancer cell motility and metastasis, this polyclonal knockout model offers a physiologically relevant system to dissect how deregulated semaphorin?CRMP pathways contribute to the aggressive behavior of kidney epithelial malignancies.
The DPYSL2 Knockout 786-O Polyclonal Cells are suited for a range of mechanistic and phenotypic investigations. Researchers can assess total and site?specific CRMP2 phosphorylation by western blotting, visualize microtubule and actin filaments via immunofluorescence, and quantify collective and single?cell motility through scratch wound healing and Transwell migration/invasion assays. Co?immunoprecipitation studies using the knockout cells as a negative control help validate CRMP2?interacting partners such as tubulin, actin, and NUMB. Additionally, this model supports pharmacologic screening for compounds that target CRMP2?modulated pathways, including Sema3A?Nrp1?Plexin signaling and GSK3???mediated phosphorylation, in a tumor?relevant epithelial background. For further information, please contact Ascent Research.
