ATG5 (Autophagy Related 5)

The SDE2-ATG5 axis serves as a critical regulator of the autophagy-ferroptosis crosstalk in MM. Targeting SDE2 restores ATG5-dependent autophagy, activates ferroptosis, and inhibits tumor growth. These findings suggest a novel therapeutic strategy that combines SDE2 inhibitors with autophagy agonists, potentially offering clinical benefits in MM treatment. This study provides further insight into autophagy-dependent ferroptosis in other malignancies.

Similarly, in the Rat Insulin Promoter T antigen pancreatic neuroendocrine tumor (RT2-PNET) model, endothelial cell deletion of Atg12 promotes liver micro-metastases. Taken together, these results from distinct preclinical cancer models reveal that endothelial cell autophagy suppresses metastatic seeding and progression and broach that autophagy inhibition in host endothelial cells may adversely influence the efficacy of systemic autophagy-lysosomal pathway inhibition in the clinical oncology setting.

Mechanistically, H. pylori activated the Erk1/2 and JNK signaling pathways to induce autophagy while inhibiting other oncogenic signaling pathways. Notably, although H. pylori induces robust autophagy, further enhancement of this process using autophagy inducers attenuated gastric cancer malignancy, suggesting that further pharmacological modulation of autophagy warrants evaluation as a potential therapeutic strategy.

Our findings suggest that pulmonary exposure to SiNPs inhibits lung cancer early progression and metastasis, with the Atg5/EVs/miR-296-3p axis playing a critical role in this process. This study offers new insights into the mechanisms linking nano-bio interaction reshaped pulmonary epithelial microenvironment and lung cancer progression.

Art emerges as a clinically potential HCC therapeutic that elicits its oncosuppressive activity through WTAP/YTHDC2-mediated m6A methylation of ATG5 transcripts, thereby causes ferroptosis of HCC mediated by autophagy.

In addition, Atg5 inactivation triggered lysosomal exocytosis through an autophagy-independent effect. Thus, our findings indicated that autophagy/ATG5 deficiency in the bone microenvironment generates a favorable environment for tumor development through several mechanisms and suggested that a bone-targeted autophagy inducer could be used to delay bone metastasis appearance.

MCB-04 exerts robust anti-breast cancer activity by triggering multiple programmed cell death pathways include apoptosis, autophagy, and paraptosis primarily through ROS-mediated mitochondrial dysfunction and inhibition of c-Met-dependent oncogenic signaling. These findings position MCB-04 as a promising multi-targeted therapeutic candidate, warranting further in vivo validation and preclinical development for breast cancer treatment.

This study demonstrates that the anti-pigmentation effect of NnE and its bioactive compound, quercetin 3-O-glucuronide, is mediated through the YAP-ATG5 signaling axis and Q3Q-driven NOX4 inhibition, which establishes the mechanistic basis for their potential application in preventing UVB-induced skin pigmentation and provides a novel perspective for the development of anti-photoaging interventions.

Notably, amiodarone showed equivalent anti-tumor efficacy but with fewer side effects on the treated mice compared to the clinical anti-cancer drug Mitomycin C (MMC). Similarly, low autophagy is associated with a poor overall survival rate. Furthermore, repurposing amiodarone-induced autophagy accompanied by trivial side effects shows potential for the treatment of bladder cancer patients.

Although apoptosis is eventually induced in TM3 cells, protective autophagy is also activated to mitigate the cytotoxic impact of the combination treatment. This finding may provide a reference for the development of safe therapeutic regimen for Leydig cell tumors.

Both Atg5 knockdown and pharmacological inhibition of autophagy prevented DHA-induced GPX4 loss and the consequent radiosensitization. Collectively, our findings reveal a previously unrecognized mechanism in which DHA overcomes TNBC radioresistance by co-opting the autophagy pathway to degrade GPX4 and unleash ferroptosis, presenting a promising therapeutic paradigm targeting the autophagy-ferroptosis axis for refractory TNBC.