Our data suggest that ECM rigidity-mediated regulation of the YAP/TAZ-TEAD transcriptional module may be playing a key role in the tumor cell response to ER stress by controlling the activation of the TRAIL-R2/DR5-mediated signaling pathway, although the role of the Hippo pathway has not been addressed in our work. The gene discussed is TNFRSF10B; the disease is neoplasm.