ATF6 Knockout CAL-27 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human CAL-27 tongue squamous cell carcinoma line. This product comprises a mixed pool of cells carrying diverse gene-disrupting mutations at the ATF6 locus, introduced by CRISPR/Cas9-mediated genome editing. The polyclonal format minimizes clonal artifacts and provides a broadly representative loss-of-function model for studying ATF6 signaling in an epithelial carcinoma context. It is supplied as a cryopreserved population ready for expansion and experimentation.
The CAL-27 cell line is an adherent epithelial model isolated from a human oral squamous cell carcinoma, characterized by aggressive tumor behavior and high metastatic potential. These cells are widely used to investigate cancer cell survival, drug resistance, and stress responses. Their epithelial carcinoma origin makes them particularly relevant for dissecting the unfolded protein response (UPR) in solid tumors subjected to microenvironmental stressors such as hypoxia, nutrient deprivation, and therapeutic agents.
ATF6 encodes a transmembrane transcription factor that acts as a central UPR regulator. Upon ER stress, ATF6 dissociates from BiP/GRP78 and traffics to the Golgi, where it is cleaved by site-1 (MBTPS1) and site-2 (MBTPS2) proteases, releasing the active N-terminal fragment (p50). Nuclear p50 transcriptionally upregulates ER chaperones (BiP/GRP78), folding enzymes, and ER-associated degradation (ERAD) components such as HERPUD1 and EDEM1. It also promotes expression of XBP1 and CHOP/DDIT3, linking to the IRE1?? and PERK branches of the UPR. ATF6 activity is triggered by diverse ER stressors including tunicamycin, thapsigargin, and hypoxia, and is modulated by interactions with ATF6?? and CREB3 family members.
In squamous cell carcinoma, ATF6-driven UPR signaling facilitates tumor adaptation to proteotoxic stress, contributing to drug resistance and metastatic progression. Disruption of ATF6 in CAL-27 cells thus generates a critical tool for examining how carcinoma cells rely on this pathway for survival and therapeutic escape. This polyclonal knockout model allows interrogation of the functional consequences of ATF6 loss on proliferation, apoptosis, and sensitivity to ER stress-inducing agents, as well as exploration of synthetic vulnerabilities with other UPR components.
This product supports detailed mechanistic studies using Western blotting to track ATF6 cleavage (p90 to p50), RT-qPCR for UPR target genes (BiP, CHOP, XBP1), and immunofluorescence to monitor nuclear translocation. Reporter assays with UPRE-luciferase quantify ATF6 transcriptional activity, while cell viability and flow cytometry assays under tunicamycin challenge assess stress adaptation and apoptosis. The polyclonal format is ideal for high-throughput screening of ER stress modulators. For additional information, please contact Ascent Research.
