Fig. 7. SPARC reduces the tolerance to ER stress in CRC cells.

SPARC interferes with the binding between GRP78 and ER stress sensors (such as PERK and IRE1α) via its interaction with GRP78. Under ER stress, the stress stimulus is amplified in high SPARC-expressing cells, as SPARC facilitates the dissociation of GRP78 from the ER stress sensors, thereby lowering the threshold of ER stress signaling and subsequent activation of the apoptotic cascade