ATG7 (Autophagy Related 7)

Our findings demonstrate that luteolin induces autophagy-dependent ferroptosis in HCC by suppressing SLC40A1-dependent Fe2+ export. This study uncovers a novel anti-tumor mechanism of luteolin, providing a potential therapeutic strategy for HCC treatment by targeting SLC40A1-mediated iron homeostasis and the crosstalk between autophagy and ferroptosis.

This mechanism establishes a new paradigm of tumor-host systemic communication, wherein circulating tumor-derived mitochondria might actively influence disease progression. These findings open avenues for developing non-invasive biomarkers and therapeutic strategies targeting mitochondrial release.

Significant prolongation of cardiac allograft survival might be achieved by suppressing the activity of cardiofibroblasts, which could be effectively regulated by targeting fibroblastic ATG5, a critical component of autophagy.

In FLT3-ITD AML cell lines (MOLM13 and MV4-11), treatment with first- and second-generation FLT3i (midostaurin and quizartinib, respectively) induced autophagy. The combination of quizartinib and chloroquine demonstrated a synergistic effect in MV4-11QR cells and this effect was associated with greater inhibition of the FLT3 receptor compared to the monotherapies. Therefore, combining FLT3i with autophagy inhibition enhances the FLT3i antileukemic efficacy and overcomes pharmacological resistance.

Our data thus reveal for the first time that TGF-β regulates CD8+ T cell memory by triggering mTORC1Weak-mediated activation of the transcriptional FOXO1-TCF1-Eomes and metabolic AMPK-ULK1-ATG7 pathways. Given that induction of more qualified CD8+ TM cells is one of the ultimate goals of vaccination, our findings identify additional targets critical to TGF-β-induced T cell memory, which may greatly impact future vaccine development for the treatment of cancer and infectious diseases.

CPNE3 promotes CRC progression by interacting with KIF4 and regulating PI3K/AKT/mTOR and autophagy pathways. The CPNE3-KIF4 axis is a potential therapeutic target.

Notably, improving nutrition in mice with disrupted muscle autophagy promotes tumor growth. Together, the data argue that early peripheral tissue wasting associated with early pancreatic cancer is driven by altered normal pancreatic organ function that leads to reduced nutrition and enhanced muscle autophagy, releasing nutrients to support both tumor and host metabolism.

These findings highlight ATR inhibition as a unique therapeutic strategy that simultaneously disrupts DDR signaling and autophagy, thereby enhancing CIS sensitivity. Targeting ATR could reduce the required CIS dosage, limit treatment-associated toxicity, and ultimately improve survival and clinical outcomes for OS patients.

In addition to all important results, in ovo HET-CAM analysis also revealed that both molecule 4 and molecule 6 were non-irritant, as no hemorrhage, vascular lysis, or coagulation was observed, resulting in an irritation score of zero. This favorable tolerability profile indicates the absence of acute membrane toxicity and supports the suitability of these molecules for further biological evaluation.

Levels of inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) were significantly elevated in all three screens, with complement C5, complement factors B and H (CFB/CFH), and monocyte differentiation antigen CD14 increased in KPC mice and PDAC patients; and all were significantly increased co-ordinately in PDAC according to disease stage. Serum levels of C5, CFH and CD14 together constitute a novel panel for identifying PanINs and early-stage PDAC with confidence, and when combined with additional screening, could help increase survival from this dismal disease.

In vivo, perivascular delivery of PDK4-IN-1 in the mouse carotid artery injury model significantly ameliorated neointimal hyperplasia. Inhibition of PDK4 perturbs pathological VSMC phenotypic switching, suppresses proliferation, promotes apoptosis and autophagy, and mitigates neointimal formation, highlighting PDK4 as a promising therapeutic target for vascular proliferative diseases.

Finally, we discuss potential therapeutic strategies, including Proteolysis Targeting Chimeras (PROTACs), dual E3 ligase/autophagy inhibitors, and autophagy flux modulators, to overcome resistance and enhance treatment efficacy across multiple cancer types. These insights establish the foundation for targeting the ubiquitin-autophagy network as a cohesive strategy to combat refractory cancer.