Unravel the molecular mechanism of XBP1 in regulating the biology of cancer cells

Cancer cells are usually exposed to stressful environments, such as hypoxia, nutrient deprivation, and other metabolic dysfunctional regulation, leading to continuous endoplasmic reticulum (ER) stress. As the most conserved branch among the three un-folded protein response (UPR) pathways, Inositol-requiring enzyme 1 alpha (IRE1 alpha)-X-box-binding protein 1 (XBP1) signaling has been implicated in cancer development and progression. Active XBPI with transactivation domain functions as a transcription factor to regulate the expression of downstream target genes, including many oncogenic factors. The regulatory activity of XBP1 in cell proliferation, apoptosis, metastasis, and drug resistance promotes cell survival, leading to tumorigenesis and tumor progression. In addition, the XBP1 peptides-based vaccination and/or combination with immune-modulatory drug administration have been developed for effective management for several cancers. Potentially, XBP1 is the biomarker of cancer development and progression and the strategy for clinical cancer management.