Figure 3.

Dual roles of inositol-requiring enzyme 1 (IRE1)/X-box binding protein 1 (XBP1) in estrogen receptor 1 (ESR1)+ breast cancers and triple negative breast cancer (TNBC). Both XBP1 isoforms can activate ESR1 signaling in ESR1+ breast cancer cells and facilitate estrogen (E2)-independent tumour survival and proliferation. ESR1 signaling promotes expression of XBP1, thus generating a feed-forward mechanism. In TNBC cells, IRE1 exhibits high basal activity and activates XBP1s which dimerises with hypoxia inducible factor 1 subunit alpha (HIF1α) potentiating the expression of hypoxia response genes. This signaling drives tumour growth and angiogenesis (Lower panel adapted from Chen et al. [9]).