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. Author manuscript; available in PMC: 2018 May 21.
Published in final edited form as: Sci Signal. 2017 Jun 6;10(482):eaah7177. doi: 10.1126/scisignal.aah7177

Fig. 8. Model of TERS-mediated signaling in cancer cells.

Fig. 8

We propose a model in which cancer cells exposed to TERS undergo an adaptive UPR that involves diverse signaling events. One effect is the activation of Wnt signaling. TERS drives Wnt signaling through the activation of the TCF. This effect appears to be IRE1α-dependent. The other relevant event is cytoprotection. In this case, TERS engages PERK but also leads to reduced ATF4 activation. Reduced levels of ATF4 are insufficient to drive full activation of apoptosis through the downstream CHOP target (red strikethrough). In this respect, ATF4 serves as a rheostat for cell survival. TERS also increases the amounts of GRP78, both intracellularly and at the cell surface. Finally, TERS induces the export of TERT to the cytoplasm. These effects, possibly in combination, promote cytoprotection and, ultimately, cell fitness to endogenous (nutrient) and exogenous (chemotherapeutic) stress.