CCM2 Knockout HeLa Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal population of HeLa cells with disruption of the CCM2 gene. This heterogeneous knockout model provides a robust system for loss-of-function studies without the limitations of clonal selection, enabling analysis of CCM2-dependent cellular processes in an epithelial context.
HeLa cells are an immortalized human cervical adenocarcinoma line positive for HPV18 and characterized by aneuploidy. Their epithelial phenotype and extensive use in cancer research make them a relevant host for interrogating cell adhesion, migration, and signaling pathways governed by CCM2.
CCM2 is a scaffold protein within the CCM complex, together with CCM1 (KRIT1) and CCM3 (PDCD10). It interacts with ICAP1 and MEKK3, linking upstream activators such as RAP1A and integrin ??1 to downstream signaling modules. CCM2 loss destabilizes the complex, leading to unchecked MEKK3-mediated ERK5 phosphorylation via MEK5 and aberrant RhoA-ROCK signaling. This dysregulation compromises actin cytoskeletal dynamics and junctional protein networks involving VE-cadherin and ??-catenin, ultimately impairing epithelial barrier function.
In HeLa cells, CCM2 knockout provides a platform to study how the CCM complex regulates epithelial integrity and how its disruption interfaces with HPV18-associated oncogenic pathways. The model recapitulates key signaling defects observed in cerebral cavernous malformations, offering a simplified epithelial surrogate for mechanistic dissection.
Applications include exploring CCM pathway signaling, cell adhesion and migration assays, and drug screening for CCM modulators. Western blotting for CCM2, phospho-ERK5, and phospho-MLC validates knockout and downstream effects, while immunofluorescence for E-cadherin and ??-catenin, coupled with RhoA activation assays, assesses junctional and cytoskeletal changes. Contact Ascent Research for additional details.
