The CCDC97 Knockout NCI-H1975 Polyclonal Cells are a pooled population of CRISPR/Cas9-edited human lung adenocarcinoma epithelial cells carrying targeted disruption of the CCDC97 gene. This product provides a heterogeneous loss?of?function model that avoids the bottleneck of single?cell clonal selection, making it ideal for robust functional genomics and drug?response studies. CCDC97 encodes a coiled?coil domain?containing protein that promotes oncogenic phenotypes, and its knockout enables systematic dissection of PTEN/AKT?dependent signaling in cancer.
The host NCI?H1975 cell line was derived from a 62?year?old female never?smoker with lung adenocarcinoma and harbors both an activating EGFR L858R mutation and the T790M gatekeeper mutation. These dual mutations confer resistance to first? and second?generation EGFR tyrosine kinase inhibitors, and the line is widely used to model acquired drug resistance and evaluate next?generation TKIs. NCI?H1975 cells display adherent, epithelial morphology and retain key features of EGFR?mutant non?small cell lung cancer.
CCDC97 functions as a positive regulator of AKT/mTOR signaling by suppressing the tumor suppressor PTEN. CCDC97 knockdown leads to upregulation of PTEN, which dephosphorylates and inactivates AKT at Ser473, thereby attenuating downstream mTOR/S6K activity and cyclin D1 expression. This pathway convergence reduces cell proliferation, migration, and invasion. Additional downstream mediators include the cyclin?dependent kinase inhibitors p21 and p27, which enforce cell cycle arrest upon CCDC97 disruption. The upstream mechanisms controlling CCDC97 expression remain poorly defined, but its effects on PI3K/AKT/mTOR signaling position it as a candidate oncogenic modulator.
In the NCI?H1975 background, CCDC97 knockout permits direct interrogation of how PTEN/AKT pathway interactions influence EGFR?driven TKI resistance. Because these cells inherently rely on sustained PI3K/AKT activity, ablating CCDC97 can reveal synthetic vulnerabilities and compensatory rewiring events. The polyclonal composition preserves natural genetic heterogeneity, enabling researchers to study population?level signaling adaptations and drug?response distributions that are more representative of clinical tumor biology.
Typical applications include western blotting for PTEN, phospho?AKT (Ser473), and phospho?S6K to verify pathway alterations; cell proliferation (MTT/BrdU) and colony formation assays; transwell migration/invasion assays to assess metastatic potential; flow cytometric cell cycle profiling for G1/S checkpoint changes; and xenograft tumor models for in vivo efficacy studies. This knockout model serves as a focused platform to explore therapeutic strategies targeting the PTEN/AKT axis in EGFR?mutant lung adenocarcinoma. For additional details, technical assistance, or pricing inquiries, please contact Ascent Research.
