The ATF6 Knockout 143B Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population featuring disruption of the ATF6 gene in the 143B human osteosarcoma background. This heterogeneous pool provides a loss-of-function model to study ATF6-dependent processes without the clonal artifacts of single-cell-derived lines.
The 143B cell line is a tumorigenic and highly metastatic osteosarcoma model, derived from HOS cells. It recapitulates malignant bone-forming properties and is widely used for investigating osteosarcoma pathogenesis and mechanisms of bone metastasis, particularly cellular adaptations that support tumor progression and resistance to therapy.
ATF6 is an ER stress sensor and transcription factor that governs the adaptive unfolded protein response (UPR). Under basal conditions, ATF6 is retained in the ER by BiP/GRP78. ER stress triggers BiP dissociation, allowing ATF6 transport to the Golgi, where it is cleaved by S1P and S2P proteases. The released N-terminal domain enters the nucleus, interacts with coactivators such as CBP/p300, and induces expression of ER chaperones including GRP78, GRP94, and calreticulin, as well as XBP1, EDEM1, and the pro-apoptotic factor CHOP. ATF6 operates in concert with IRE1?? and PERK pathways to restore ER homeostasis. Key interacting partners include importins for nuclear import and general transcription factors that facilitate target gene activation.
In 143B osteosarcoma cells, ATF6 disruption impairs the adaptive UPR, heightening sensitivity to ER stress from hypoxia, nutrient deprivation, or chemotherapeutic agents. Since proteostatic robustness supports osteosarcoma survival and metastasis, loss of ATF6 compromises stress resilience and may influence tumor cell proliferation, apoptosis, and invasive behavior. This model enables dissection of UPR-dependent survival mechanisms in bone cancer and assessment of ATF6 as a candidate therapeutic target.
Researchers can use these cells for diverse UPR-focused assays. Western blotting of ATF6, GRP78, and CHOP, along with RT-qPCR for GRP78, XBP1, and CHOP, quantifies UPR activation. Luciferase reporters with ERSE elements measure ATF6 transcriptional output, while immunofluorescence tracks ATF6 trafficking after exposure to ER stress inducers such as tunicamycin. Functional studies include cell viability, apoptosis, and migration/invasion assays. For further details, contact Ascent Research.
