Single-nuclei UPR profiling by FACS reveals bortezomib resistance mechanisms in multiple myeloma

ABSTRACT: The unfolded protein response (UPR) is a stress-adaptation pathway and therapeutic target in cancer, yet its pro-survival versus pro-death outcome is difficult to predict because the three ER sensors, PERK, IRE1α and ATF6, are highly interconnected. Transcriptomic analyses identified sensor-specific gene signatures associated with patient survival across malignancies, and indicated that low IRE1α activity (low XBP1 signature or higher expression of RIDD targets) correlates with improved outcome. We developed SNUPR (single nuclei analysis of the unfolded protein response), an accessible flow-cytometry approach that profiles all three branches in nuclear suspensions. SNUPR reveals marked heterogeneity of UPR activation across cancer cell lines that cannot be inferred from sensor expression.

SUBMITTER: Julien, Paul Gigan 

PROVIDER: S-SCDT-10_1038-S44321-026-00469-7 | biostudies-other |

REPOSITORIES: biostudies-other