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Metastasis is a major contributing factor that affects the prognosis of melanoma patients. Nevertheless, the underlying molecular mechanisms involved in melanoma metastasis are not yet entirely understood. Here, we identified ubiquitin‐specific protease 22 (USP22) as a pro‐oncogenic protein in melanoma through screening the survival profiles of 52 ubiquitin‐specific proteases (USPs). USP22 demonstrates a strong association with poor clinical outcomes and is significantly overexpressed in melanoma. Ablation of USP22 expression remarkably attenuates melanoma migration, invasion, and epithelial–mesenchymal transition in vitro and suppresses melanoma metastasis in vivo. Mechanistically, USP22 controls melanoma metastasis through the SIRT1/PTEN/PI3K pathway. In addition, we conducted an United States Food and Drug Administration‐approved drug library screening and identified topotecan as a clinically applicable USP22‐targeting molecule by promoting proteasomal degradation of USP22. Finally, we found that both pharmacological and genetic silence of USP22 sensitize RSL3‐induced ferroptosis through suppressing the PI3K/Akt/mTOR pathway and its downstream SCD, and ferroptosis inhibitor could partly rescued the decreased lung metastasis by topotecan in vivo. Overall, our findings reveal a prometastatic role of USP22 and identify topotecan as a potent USP22‐targeting drug to limit melanoma metastasis. [ABSTRACT FROM AUTHOR]

The epidemiological landscape of infantile hemangioma (IH) has been extensively explored through diverse data sources; however, a scarcity of systematically pooled and quantified evidence from comprehensive global studies persists. In this meta‐analysis, we systematically review available literature to elucidate the prevalence, distribution of lesions, complications, and risk factors associated with IH. A meticulous search encompassing the Cochrane Library, PubMed, Embase, and Web of Science identified 3206 records, of which 55 studies met the inclusion criteria. We found that the overall prevalence of IH is 2.8% [95% confidence interval (CI): 1.5–4.4%] (31,274,396 infants), and IH was located more frequently in the head and neck with a prevalence of 47.4% (95% CI: 39.5–55.4%). The overall prevalence of complications of IH is 24.3% (95% CI: 18.6–30.5%), ulceration is 16.0% (95% CI: 10.4–21.2%), bleeding is 5.6% (95% CI: 3.3–8.5%), visual impairment is 5.6% (95% CI: 3.0–8.9%), infection is 2.8% (95% CI: 1.5–4.8%), subglottic obstruction is 1.5% (95% CI: 0.5–3.0%), respectively. Through 27 studies, we have evaluated 35 factors encompassing perinatal factors, socioeconomic factors, maternal complications, drug factors, and antepartum procedures, and identified 18 risk factors that increase the prevalence of IH. These findings can greatly assist clinicians and family members in effectively evaluating the risk of IH, and determining whether pregnant women should undergo intensified monitoring or preventive measures. [ABSTRACT FROM AUTHOR]

Beclin 2 plays a critical role in metabolic regulation and obesity, but its functions in innate immune signaling and cancer development remain largely unknown. Here, we identified Beclin 2 as a critical negative regulator of inflammation and lymphoma development. Mice with homozygous ablation of BCL2-interacting protein 2 (Becn2) developed splenomegaly and lymphadenopathy and markedly increased ERK1/2 and NF-[kappa]B signaling for proinflammatory cytokine production. Beclin 2 targeted the key signaling kinases MEKK3 and TAK1 for degradation through an ATG9A-dependent, but ATG16L/ Beclin 1/LC3-independent, autophagic pathway. Mechanistically, Beclin 2 recruited MEKK3 or TAK1 through ATG9A to form a complex (Beclin 2-ATG9A-MEKK3) on [ATG9A.sup.+] vesicles upon ULK1 activation. Beclin 2 further interacted with STX5 and STX6 to promote the fusion of MEKK3- or TAK1-associated [ATG9A.sup.+] vesicles to phagophores for subsequent degradation. Importantly, Becn2-deficient mice had a markedly increased incidence of lymphoma development, with persistent STAT3 activation. Myeloid-specific ablation of MEKK3 (Map3k3) completely rescued the phenotypes (splenomegaly, higher amounts of proinflammatory cytokines, and cancer incidence) of Becn2-deficient mice. Hence, our findings have identified an important role of Beclin 2 in the negative regulation of innate immune signaling and tumor development through an ATG9Adependent, but ATG16L/Beclin 1/LC3-independent, autophagic pathway, thus providing a potential target for the treatment of inflammatory diseases and cancer., Introduction Autophagy is an essential cellular process for maintaining cell homeostasis and attenuating cell stresses through a 'self-eating' mechanism. Many autophagy-related (ATG) proteins have been identified as functioning in autophagy [...]

The supplementation of cystine also induced disulfidptosis in cancer cells with SLC7A11 low expression, accompanied by intracellular NADPH depletion, aberrant disulfide frormation in actin cytoskeleton and F-actin contraction. A recent study published in I Nature Cell Biology i demonstrated a novel type of regulated cell death (RCD) termed disulfidptosis that is caused by excessive disulfide formation in actin cytoskeleton and actin filament (F-actin) collapse, highlighting a promising anticancer strategy to target disulfidptosis [[1]]. Inhibiting NADPH depletion with cystine starvation, increasing NADPH supply with 2-deoxyglucose (2-DG), or treatment with disulfide-reducing agent 2-ME prevented the retarded migration of these actin cytoskeleton-associated proteins and disulfidptosis. [Extracted from the article]