Multi-omics analysis reveals novel roles for IRE1α in triple negative breast cancer (TNBC)

Constitutive aberrant IRE1α signalling has been previously reported in triple negative breast cancer (TNBC), where is suggested to contribute to the disease progression and therapy resistance. Despite its clinical relevance, the biological meaning of IRE1α in TNBC context and the exact mechanisms through which it contributes to the disease are not fully understood. In this thesis, while investigating IRE1α signalling contribution to TNBC biology in MDA-MB-231 cells, we identified a role for IRE1α in two distinct processes outside of canonical proteostasis function. Firstly, we identified a group of pro-inflammatory cytokines as factors regulated in an IRE1-dependent manner. Secondly, we determine that RIDD-mediated silencing of a key enzyme in TAG biosynthesis links IRE1α activity to TAG abundance and FA usage. Collectively our results support this expanded view of IRE1α function and reveal novel potential contributions to the disease phenotype in TNBC.2025-09-0