To further understand the role of the unfolded protein response (UPR) sensor IRE1α, we generated specific mutations in WT IRE1α to potentially alter its activity. We have experimentally determined the impact of the mutations under conditions of nutrient starvation by expressing them in immortalized epidermal keratinocytes in vitro. We saw that overexpression of active IRE1α hinders cell survival in tumor promoting conditions while inactivation of IRE1α aids cell survival and possibly contributes to cancer development.