ATF4 (Activating Transcription Factor 4)

Anti-LCN2 antibodies promote robust anti-tumour T cell responses in mouse models of aggressive solid tumours. Our study shows that the ATF4-LCN2 axis has a cell-extrinsic role in suppressing anti-cancer immunity, and could pave the way for an immunotherapy approach that targets LCN2.

Notably, cancer-associated fibroblasts (CAFs) reprogrammed by ISR-activated cells, shifting from myCAF to iCAF phenotype with reduced collagen synthesis and glycine-to-serine conversion, produced serine and sustained tumor growth in amino acid-depleted environments. Our findings demonstrate the power of translatome profiling to reveal stable, drug-resistant PDA cell states and identify a targetable CAF-tumor metabolic symbiosis, opening new avenues for therapeutic intervention in this highly lethal malignancy.

Despite distinct organelle localizations, both genes converge on a shared immunometabolic pathways, revealing a coordinated ER-mitochondria axis that shapes viral expression and immune signaling. These findings provide new insights into the roles of host antiviral effectors and uncover potential targets for modulating EBV activity in inflammatory and oncogenic contexts.

Distinct pathogenic NLS mutations of FUS differentially regulate cellular stress responses through different mechanisms, contributing to ALS initiation and progression. Among these, FUSP525L promotes the formation of larger stress granules, whereas FUSR514S more readily activates the cellular ISR.

Lastly, ZFAS1 suppression decreased cell viability both at baseline and in response to acute thapsigargin treatment. This work identifies novel ZFAS1 variants and uncovers a link between ER stress and ZFAS1 through the UPR.

Furthermore, depletion of BCLAF1 sensitizes AML cells to venetoclax, a clinically relevant BCL-2 inhibitor...Aberrant RNA splicing and metabolic reprogramming are hallmarks of cancer, yet how these processes are mechanistically linked remains unclear. This study identifies BCLAF1 as a key regulator connecting splicing control to amino acid metabolism in acute myeloid leukemia, revealing a previously unrecognized functional vulnerability at the intersection of these pathways.

Finally, NXP800 delays tumor growth in preclinical OS model by promoting apoptosis. This study is a preclinical proof-of-principle of therapeutic efficacy of NXP800 both in vitro and in vivo, highlighting the relevance of targeting GCN2, and consequently activating the ISR and UPR, to induce apoptosis and inhibit tumor progression in OS.

Repurposed drugs such as flubendazole and the ezetimibe derivative L14-8, along with natural compounds including evodiamine and luteolin, demonstrate translational potential for ferroptosis induction. Collectively, ferroptosis represents a promising therapeutic vulnerability for precision treatment of advanced prostate cancer.

Buf-ZIF-lipo-SP94 achieved synergistic effects with anti-PD-L1 for HCC immunotherapy, showing better tumor inhibition rate (>90 %), survival of animals and safety. This study uncovered the potential of Buf in inducing ICD and downregulating PD-L1 expression, developing a Buf-loaded nanovaccine for combination strategy of immunotherapy in HCC.

This study examined the effects of five anticancer agents-cisplatin, 5-fluorouracil, vincristine, irinotecan, and cyclophosphamide-on mouse skeletal muscle. Targeting ER stress may help prevent chemotherapy-induced muscle wasting. Further studies are needed to clarify mechanisms and develop protective strategies.

These findings support a model in which CBD downregulates HER2 and, in a HER2-dependent context, promotes paraptosis and ferroptosis. In addition, docking and molecular dynamics analyses suggested a potential interaction between CBD and HER2, providing mechanistic insights into possible molecular recognition relevant to HER2-positive breast cancer.

In conclusion, our findings indicate that CDA induces sustained ER stress, thereby activating the PERK/ATF4/CHOP pathway to trigger apoptosis in HeLa cells. Together, these findings define CDA as a novel marine-derived depsidone scaffold that induces apoptosis via sustained ER stress signaling and provides a basis for future structure optimization.