The CCM2 Knockout A-549 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the CCM2 gene in A-549 human lung adenocarcinoma epithelial cells. This model enables loss-of-function studies of CCM2, a scaffold protein central to junction integrity and signaling. The polyclonal format avoids clonal artifacts, providing a robust system for functional genomics.
A-549 cells originate from alveolar basal epithelial adenocarcinoma and serve as a standard model for lung cancer and epithelial biology. Their adherent epithelial phenotype and well-documented characteristics make them suitable for dissecting pathways governing cell adhesion, migration, and barrier function.
CCM2 scaffolds a complex with KRIT1 (CCM1) and PDCD10 (CCM3) that suppresses RhoA-ROCK signaling and modulates MEKK3-MEK5-ERK5 cascades. Upstream inputs from HEG1, integrins, VEGF, BMP, and ICAP1 converge on CCM2, while downstream effectors encompass RhoA, ROCK, ERK5, p38 MAPK, VE-cadherin, and MLCK. CCM2 interacts directly with ICAP1, MEKK3, and Rap1 to coordinate actin dynamics and cadherin-mediated adhesion. Loss of CCM2 disrupts this network, leading to Rho-ROCK hyperactivation and aberrant ERK5 activity, compromising cell?Ccell contacts.
In A-549 cells, CCM2 ablation permits investigation of junctional destabilization, cytoskeletal remodeling, and altered Rho/ERK5 signaling relevant to both cerebral cavernous malformation pathophysiology and cancer. The epithelial context allows examination of CCM2??s role in E-cadherin organization, collective migration, and barrier integrity, providing insights into mechanisms that may underlie metastatic dissemination or vascular lesion formation.
Typical applications include western blotting for CCM2 and junction markers, immunofluorescence for E-cadherin and actin, transwell migration assays, Rho-GTP pull-downs, co-immunoprecipitation, RT-qPCR for adhesion transcripts, and TEER barrier measurements. These cells support research in cerebral cavernous malformations, Rho signaling, drug screening, and cancer metastasis. For inquiries, please contact Ascent Research.
