The DPYSL2 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population with targeted disruption of the DPYSL2 gene, encoding collapsin response mediator protein 2 (CRMP2). This loss-of-function model provides a heterogeneous pool of knockout cells for investigating CRMP2 function in a lung adenocarcinoma background.
NCI-H1975 is a human lung adenocarcinoma cell line derived from a non-smoking female, harboring EGFR L858R and T790M mutations. It serves as a key non-small cell lung cancer (NSCLC) model with acquired resistance to first-generation EGFR inhibitors, retaining epithelial characteristics and EGFR-driven signaling relevant to metastasis studies.
DPYSL2/CRMP2 is a microtubule-associated protein critical for cytoskeletal reorganization, axon guidance, and cell migration. It is phosphorylated by Cdk5 and GSK3?? downstream of Sema3A/PlexinA, and modulated by RhoA and Ca2+/calmodulin-dependent kinase II. CRMP2 interacts with tubulin, actin, kinesin-1 (KIF5), other CRMP family members (DPYSL1,3,4,5), Numb, and endophilin to regulate microtubule assembly, actin filament organization, and focal adhesion turnover. Through these interactions, CRMP2 transduces extracellular guidance cues into directional cell motility.
In the context of NCI-H1975, CRMP2??s role in cell migration and invasion is especially relevant for studying metastatic dissemination of EGFR-mutant lung adenocarcinoma. Cross-talk between EGFR signaling and CRMP2-regulatory kinases such as Cdk5 and GSK3?? may modulate CRMP2 phosphorylation, thereby affecting its ability to organize microtubules and actin filaments. Given the dual tumor-suppressive and oncogenic potential reported for CRMP2, this polyclonal knockout provides a critical tool to clarify its function in NSCLC. Loss of CRMP2 is anticipated to destabilize microtubules and disrupt semaphorin-mediated signaling, potentially attenuating cell motility and invasiveness.
This polyclonal DPYSL2 knockout cell population enables detailed investigation of lung adenocarcinoma metastasis and cell migration mechanisms. Researchers can employ functional assays such as wound healing and Transwell migration/invasion to quantify motility, immunofluorescence and live cell imaging to visualize cytoskeletal dynamics, and Sema3A stimulation to probe CRMP2-dependent signaling. Gene disruption is verifiable by Western blot for DPYSL2 and phospho-CRMP2, RT-qPCR, and Sanger sequencing or next-generation sequencing for editing efficiency. The model also supports drug response evaluation in EGFR-mutant NSCLC. For additional information or to inquire about customization, please contact Ascent Research.
