Numerous studies have recently pointed out that communication of the extracellular matrix (ECM) with surrounding tumor cells dictates in part UPR activity and vice versa. In the context of this dynamic interplay, ER stress and UPR mechanisms have been proposed as potential targets to elicit novel and effective therapeutic approaches in clinical trials.

Surprisingly, we found that HaloPROTAC3 results in UPR activation in non-engineered mammalian cells. Our data demonstrate that HaloPROTAC3 causes mild endoplasmic reticulum stress independent of IGF2BP3 function and shall guide future studies using the HaloPROTAC3 protein depletion strategy.

Herein we report ErSO-TFPy as a small molecule that induces quantitative or near-quantitative regression of tumors in multiple mouse models of breast cancer with a single dose...Mechanistically, these tumor regressions are a consequence of rapid induction of necrotic cell death in the tumor and are immune cell independent. If successfully translated to human cancer patients, the benefits of such an anticancer drug that is effective with a single dose would be significant.

Such an effect contributed to mechanistic target of rapamycin (mTOR)-phosphorylated eukaryotic translation initiation factor 4E-binding protein 1 (p-4EBP1) axis inhibition, also occurring through c-Myc downregulation. However, besides the pro-death effects, JQ-1/Bortezomib activated UPR and autophagy as pro-survival mechanisms. In conclusion this study demonstrates that JQ-1/Bortezomib combination could be a promising treatment for MM and PEL, unveiling new molecular mechanisms underlying its cytotoxic effect and suggests that UPR and autophagy inhibition could be exploited to further potentiate the cytotoxicity of JQ-1/Bortezomib.

Knockdown of key molecules in a lockstep manner directly affects the most downstream autophagy pathways in transforming cells. Overall, this study demonstrates that assembly of NOX1 complex proteins is indispensable for Cd-induced persistent ROS and controls ER stress-induced defective autophagy in mice and humans.

we constructed the first eIF2B mutant cerebral organoids to explore the dynamic brain development process, which provides a platform for further research on the specific pathogenesis of VWM.

Additionally, the synergized therapeutic effect of SIRT7 suppression and anti-PD-1 immune checkpoint blockade was also investigated. Taken together, SIRT7 can be employed as a promising target to restrain tumor growth and increase the effect of melanoma immunotherapy.

Although IRE1-knockout in HCT116 cells unexpectedly did not affect tumor growth in nude mice, IRE1-knockout HCT116 cells with ATF6α knockdown grew significantly more slowly than wild-type or IRE1-knockout HCT116 cells. These results have unraveled the situation-dependent differential compensation strategies of ATF6α.

Mechanistically, ER stress induced activation of unfolded protein response (UPR) pathways and activation of the MAPK (JNK and ERK) pathway, all of which were critical for KWM-induced apoptosis and paraptosis. These findings suggested the possibility that KWM might be considered as a potential lung cancer therapeutic agent.

In tamoxifen-resistant LY2 cells, IPAG caused Sig1R to aggregate and co-localise with the stress marker BiP. These findings showcase the potential of Sig1R as a novel biomarker in TNBC as well as highlight its ligand-induced interference with the stress-coping mechanisms of BCa cells.

In this study, we utilized ER stress-inducing reagent, thapsigargin (TG), to induced pharmacologic ER stress in lung cancer cells...In addition, PDK1-induced Snail was dependent on the lactate production derived from metabolic reprogramming. Our findings reveal a critical role of lactate in pro-invasion events and establishes a direct connection between ER-stress and metabolic reprogramming in facilitating cancer cell progression.