The CCM2 Knockout K-562 Polyclonal Cells constitute a CRISPR/Cas9-edited polyclonal knockout cell population, generated by targeted disruption of the CCM2 gene in the K-562 human chronic myelogenous leukemia (CML) cell line. This product provides a genetically defined loss-of-function model for investigating CCM2-dependent signaling mechanisms within a hematopoietic context. The polyclonal population retains heterogeneity, enabling robust analysis of gene function without clonal selection artifacts.
K-562 cells were originally derived from the pleural effusion of a patient with CML in blast crisis and harbor the Philadelphia chromosome, resulting in constitutive BCR-ABL tyrosine kinase activity. Widely employed as a model system for hematopoietic cell differentiation and leukemia biology, K-562 cells are particularly suited for studying signal transduction pathways relevant to proliferation, apoptosis, and cell adhesion. Their suspension growth properties facilitate high-throughput genetic manipulation and functional assays.
CCM2 (cerebral cavernous malformation 2) is a core scaffold protein of the CCM complex, directly interacting with KRIT1 (CCM1) and PDCD10 (CCM3). The ternary complex negatively regulates RhoA-ROCK and MEKK3-MAPK cascades to maintain endothelial barrier integrity and control cytoskeletal remodeling. CCM2 couples upstream signals from VEGFR2, KLF2/4 transcription factors, and integrin engagement to downstream effectors including ERK1/2, JNK, p38 MAP kinases, and RhoA GTPase. Disruption of CCM2 results in unchecked MEKK3?CERK activation and elevated RhoA activity, leading to increased cell contractility, expression of adhesion molecules ICAM-1 and VCAM-1, and production of matrix metalloproteinases MMP-2 and MMP-9. This signaling hub integrates VEGF, WNT/Frizzled/LRP5/6, and shear stress pathways, placing CCM2 at the center of vascular homeostasis regulation.
Although CCM2 function is predominantly characterized in endothelial cells, its expression and role in hematopoietic lineages are increasingly recognized. In K-562 cells, CCM2 knockout enables dissection of MAPK and Rho GTPase signaling in a BCR-ABL-driven background, offering a unique platform to explore crosstalk between oncogenic and developmental signaling networks. The model is valuable for assessing how CCM2 loss alters the phosphorylation landscape, cell adhesion dynamics, and migratory behavior in a leukemic context, and may reveal vulnerabilities relevant to vascular anomalies and hematologic malignancies.
These polyclonal knockout cells are optimally suited for research applications including Western blot validation of CCM2 depletion, RhoA activation assays, and phospho-profiling of downstream kinases (ERK, p38). Additional uses encompass flow cytometric analysis of ICAM-1/VCAM-1, migration and adhesion assays, RNA-seq, and drug sensitivity testing with MAPK inhibitors. They also support functional genomics and synthetic lethal screens for cerebral cavernous malformation and vascular disorder research. For further details, contact Ascent Research.
