MedComm – Oncology最新文献

{"title":"β-Catenin/TCF4 Is Required for DDX17-Induced Epithelial–Mesenchymal Transition and Metastasis in Hepatocellular Carcinoma","authors":"Chaoxiang Lv,&nbsp;Na Luo,&nbsp;Yuanning Luo,&nbsp;Qiqi Zhang,&nbsp;Xiuhua Cao,&nbsp;Jingliang Cheng,&nbsp;Chunli Wei,&nbsp;Qingxi Guo,&nbsp;Kan Guo,&nbsp;Zhiqiang Mei,&nbsp;Xiaoyan Liu,&nbsp;Junjiang Fu","doi":"10.1002/mog2.70039","DOIUrl":"https://doi.org/10.1002/mog2.70039","url":null,"abstract":"<p>The DEAD-box RNA helicase 17 (DDX17) is strongly linked to the occurrence and development of specific human cancers, emphasizing its previously unrecognized biological roles in cancer progression and metastasis. However, the precise mechanisms by which DDX17 regulates liver cancer metastasis have not been thoroughly explored. In this study, increased DDX17 expression levels showed a robust association with the invasive potential of hepatocellular carcinoma (HCC) cells. Silencing DDX17 expression resulted in substantial reduction of HCC cell migration and invasion potentials, while DDX17 overexpression had the opposite effect. Silencing DDX17 also attenuated epithelial–mesenchymal transition (EMT) in HCC cells and significantly reduced metastatic lesions in an orthotopic HCC nude mouse model. Mechanistically, chromatin immunoprecipitation assays revealed that TCF4 physically interacts with the DDX17 promoter, activating its transcriptional expression. Immunoprecipitation results demonstrated that DDX17-mediated nuclear input of β-catenin is dependent on its helicase functional domain. Furthermore, we demonstrated that β-catenin/TCF4 is essential for DDX17-induced migration and invasion in HCC cells. Taken together, these findings emphasize the significance of DDX17 in the malignant progression and metastasis of HCC, revealing a novel mechanism involving the β-catenin/TCF4/DDX17 pathway.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"4 3","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Epstein–Barr Virus Envelope Glycoprotein BALF4 Promotes the Ubiquitination and Degradation of RNA Acetyltransferase NAT10 Suppressing Gastric Cancer Progression","authors":"Tianle Qiu,&nbsp;Chenbin Chen,&nbsp;Xiangwei Sun,&nbsp;Yuanbo Hu,&nbsp;Bujian Pan,&nbsp;Jun Xu,&nbsp;Jian Wen,&nbsp;Xian Shen,&nbsp;Xiangyang Xue,&nbsp;Xiaodong Chen","doi":"10.1002/mog2.70040","DOIUrl":"https://doi.org/10.1002/mog2.70040","url":null,"abstract":"<p>Epstein–Barr virus-associated gastric cancer (EBVaGC) is a unique subtype of gastric cancer (GC) with distinct molecular characteristics that generally has a better prognosis. <i>Bam</i>HI-A leftward frame 4 (<i>BALF4</i>), an envelope glycoprotein encoded by the Epstein-Barr virus (EBV), plays an important role in EBV infection. However, its biological function and potential molecular mechanisms in EBVaGC remain unclear. This study aimed to investigate the impact of the highly expressed viral gene <i>BALF4</i> on the progression of EBVaGC. Here, we detected the expression of BALF4 in GC tissue chips and validated that the presence of BALF4 might be associated with a favorable prognosis in EBVaGC. The results showed that BALF4 inhibited the proliferation, migration, and invasion of GC cells in vitro and in vivo. In addition, we discovered that BALF4 interacts with N-acetyltransferase 10 (NAT10). High expression of NAT10 in GC tissues promotes the malignant phenotype of GC cells. We discovered that BALF4 could inhibit the malignant progression of GC by promoting the ubiquitination and degradation of NAT10. In summary, our study revealed a possible mechanism explaining the favorable prognosis of the EBVaGC subtype, which contributes to a better understanding of this special type of GC.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"4 3","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactate: A Key Promoter of Cancer Stem Cells and Implications for Cancer Therapy","authors":"Yan Xue,&nbsp;Lin-Zhu Zhang","doi":"10.1002/mog2.70034","DOIUrl":"https://doi.org/10.1002/mog2.70034","url":null,"abstract":"<p>A groundbreaking study published in <i>Cell Metabolism</i> reveals how lactate promotes cancer stemness and therapy resistance by reshaping epigenetic landscapes [<span>1</span>]. By employing advanced single-cell tracking and machine learning in tumor organoids, the authors demonstrate that lactate suppresses differentiation and induces dedifferentiation of cancer cells into stem-like states through MYC activation. This discovery underscores lactate as a key regulator of tumor dynamics and identifies bromodomain protein 4 (BRD4) inhibitors as a promising therapeutic strategy to prevent relapse.</p><p>Tumor cells typically rely on glycolysis (the Warburg effect) for rapid energy supply, producing a large amount of lactate. Traditionally viewed as a metabolic byproduct, lactate is now recognized as a signaling molecule with multiple roles in the tumor microenvironment. The accumulation of lactate is closely associated with tumor proliferation, invasion, and drug resistance [<span>2</span>]. In gastric cancer, lactate promotes NBS1 K388 lactylation, enhancing MRN complex formation and recruitment to DNA double-strand breaks, thereby improving homologous recombination repair and mediating chemoradiotherapy resistance [<span>3</span>]. Lactate metabolism has thus emerged as a key focus in cancer research.</p><p>Cancer recurrence and metastasis remain major clinical challenges, driven largely by cancer stem cells (CSCs). CSCs exhibit self-renewal, multi-directional differentiation, and drug resistance, enabling survival post-therapy and tumor regeneration. Cancer differentiated cells (CDCs), as an important component of the tumor cell population, exhibit significant functional differences from CSCs. Research by the Rodríguez Colman team at the University Medical Center Utrecht revealed that murine intestinal stem cells and differentiated cells display distinct metabolic profiles and interact via lactate [<span>4</span>]. This suggests similar metabolic heterogeneity may exist between CSCs and CDCs in human intestinal tumors, with lactate playing a potential role in tumor progression. Further investigation into lactate's functional impact in these interactions is warranted.</p><p>Immunostaining of clinical samples showed that the expression level of monocarboxylate transporter 4 (MCT4), a lactate transporter, was significantly higher in CDCs than in CSCs. This indicates that CDCs have a higher glycolysis level. This finding demonstrates that, although tumor metabolism is generally characterized by the Warburg effect, there are notable differences in aerobic glycolysis levels among different tumor cell populations. Single-cell analysis further confirmed that the lactate level was elevated in CDCs relative to CSCs, indicating a higher glycolytic rate in CDCs. However, no significant differences were observed in basal glucose levels or glucose uptake between CDCs and CSCs. Interestingly, CSCs exhibited a greater capacity for lactate uptake compared to ","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"4 3","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144998988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing PD-1 Blockade With CAR-Macrophage Therapy in HER2+ Solid Tumors","authors":"Wenxue Ma,&nbsp;Catriona Jamieson","doi":"10.1002/mog2.70036","DOIUrl":"https://doi.org/10.1002/mog2.70036","url":null,"abstract":"<p>In a recent paper published in 2025 <i>Nature Communications</i>, Pierini et al. [<span>1</span>] demonstrated that chimeric antigen receptor macrophages (CAR-M) enhance the efficacy of programmed cell death protein 1 (PD-1) immune checkpoint blockade in HER2⁺ solid tumors. Using a syngeneic HER2⁺ mouse model, the study revealed that CAR-M therapy successfully reprograms the immunosuppressive tumor microenvironment (TME), promotes infiltration of CD8⁺ cytotoxic T cells (CTLs), natural killer (NK) cells, and promotes durable antigen spreading. Notably, CAR-M therapy provided protection against antigen-negative tumor relapses, a significant clinical challenge associated with current CAR-T therapies. These findings support the potential of CAR-M as a transformative adjunct to current immunotherapy strategies.</p><p>Immune checkpoint inhibitors (ICIs) targeting PD-1 or programmed death ligand 1 (PD-L1) have revolutionized cancer immunotherapy, especially in melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma. However, their limited efficacy in solid tumors is due to multiple resistance mechanisms, including a suppressive TME dominated by tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), poor antigen presentation, and inadequate T-cell infiltration. While CAR-T therapies have demonstrated remarkable success in hematological malignancies, their limited effectiveness in solid tumors remains suboptimal. These limitations underscore the urgent need for new approaches capable of overcoming immunosuppression and enhancing antigen presentation within the TME [<span>2</span>].</p><p>To overcome these challenges, CAR-M therapy represents a novel and promising immunotherapeutic modality. Macrophages are naturally equipped to infiltrate tumors, phagocytose cancer cells, and cross-present tumor antigens to the adaptive immune system [<span>3</span>]. By engineering macrophages to express a CAR targeting a tumor-associated antigen (e.g., HER2), researchers aim to redirect these cells toward tumor destruction while harnessing their innate antigen-presenting capacity. Unlike CAR-T cells, CAR-Ms are not MHC-restricted and can engage tumors through both direct cytotoxicity and activation of other immune components. This dual functionality gives CAR-M therapy a unique advantage, convert immunologically “cold” tumors into “hot,” immune-active sites.</p><p>In the HER2⁺ mouse model, Pierini et al., administered intratumoral injections of anti-HER2 CAR-M and observed a marked increase in the infiltration of CD8⁺ T cells, CD4⁺ helper T cells, NK cells, and dendritic cells (DCs) [<span>1</span>]. CAR-M treatment also reprogrammed endogenous macrophages from a M2-like, pro-tumor phenotype to an M1-like, pro-inflammatory state. Importantly, this intervention led to robust antigen spreading, a phenomenon in which T cells begin to recognize and respond to tumor antigen","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"4 3","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144998989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colorectal Cancer Cells Promote de novo Glycine Synthesis for Collagen Production in Cancer-Associated Fibroblasts by Secreting TGF-β1","authors":"Chunqi Liu,&nbsp;Huaqin Zhang,&nbsp;Jin Gong,&nbsp;Yuzhou Xiao,&nbsp;Yiyun Lin,&nbsp;Wen Peng,&nbsp;Xiaodan Pan,&nbsp;Yan Li,&nbsp;Hui Jie,&nbsp;Xinying Qian,&nbsp;Na Sang,&nbsp;Lei Tao,&nbsp;Na Su,&nbsp;Jing Wei,&nbsp;Xiaobo Cen,&nbsp;Xiao Du,&nbsp;Yinglan Zhao","doi":"10.1002/mog2.70037","DOIUrl":"https://doi.org/10.1002/mog2.70037","url":null,"abstract":"<p>Metabolic reprogramming of cancer-associated fibroblasts (CAFs) plays an important role in colorectal cancer (CRC) progression. However, the mechanisms by which dysfunctional amino acid metabolism in CAFs contributes to cancer progression remain unclear. Here, we investigated amino acid metabolism in fibroblasts derived from human CRC tissues and the molecular interactions of this regulation with CRC progression. We revealed that amino acid metabolism, especially <i>de novo</i> glycine synthesis, was significantly activated in CAFs compared with normal fibroblasts in CRC tissues. Mechanistically, transforming growth factor β1 (TGF-β1) secreted by CRC cells was identified as a key factor that induced the activation of glycine synthesis and collagen production in CAFs. The inhibition of phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in <i>de novo</i> glycine synthesis, attenuated TGF-β1-induced collagen production in CAFs. Additionally, we found that collagen levels were significantly elevated in human CRC tissues. Collectively, these findings reveal a novel mechanism by which CRC cells enhance collagen production in CAFs through TGF-β1-induced <i>de novo</i> glycine synthesis. Our data not only highlight the pivotal role of <i>de novo</i> glycine synthesis in CRC progression but also provide a potential strategy for CRC treatment by targeting PHGDH.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"4 3","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB) in Tumors and Other Diseases","authors":"Zhenyu Wu,&nbsp;Na Sun,&nbsp;Man Qu,&nbsp;Xia Kang,&nbsp;Yi Zhang,&nbsp;Xiaowei Qi","doi":"10.1002/mog2.70033","DOIUrl":"https://doi.org/10.1002/mog2.70033","url":null,"abstract":"<p>Glycoprotein non-metastatic melanoma protein B (GPNMB) is a highly conserved transmembrane glycoprotein, which is widely involved in biological processes of tissues, cells, metabolism and immunity, regulates various signaling pathways, and plays an important role in the occurrence and development of diseases. However, the effect of GPNMB on the same biological process varies greatly in different tissues, and its application as a tumor therapeutic target is also a challenge. At the same time, how to balance the multiple effects of GPNMB is also a key issue facing future clinical applications. This paper reviews the role of GPNMB in tissue repair, metabolic regulation, cell aging, immune response, and the mechanism of GPNMB's involvement in the occurrence and development of various diseases, including tumor. In this paper, we summarize the GPNMB signaling pathway, analyze its potential value as diagnostic markers and therapeutic targets, and discuss the future research direction. Through systematic summary, this review provides a theoretical basis for further understanding of the biological function of GPNMB and its role in diseases, and also provides a new idea for the formulation of GPNMB based precision treatment strategy.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"4 3","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Relationship Between Cathepsins and Breast Cancer","authors":"Xin Wang,&nbsp;Zihan Xu,&nbsp;Yiyao Zeng,&nbsp;Jie Chen","doi":"10.1002/mog2.70032","DOIUrl":"https://doi.org/10.1002/mog2.70032","url":null,"abstract":"&lt;p&gt;Cancer remains a critical global health issue, ranking as the second leading cause of death worldwide. According to the 2022 Cancer Statistics, breast cancer (BC) represents nearly one-third of all cancer diagnoses among women, with particularly high mortality rates in certain populations due to disparities in treatment access and underlying health conditions [&lt;span&gt;1&lt;/span&gt;]. While multiple factors, including genetic predispositions and environmental exposures, contribute to BC's complex etiology, the proteolytic enzyme family known as cathepsins has recently gained attention for their crucial roles in tumor biology.&lt;/p&gt;&lt;p&gt;Cathepsins play essential roles in cellular metabolism, proliferation, and tissue homeostasis. Among this family, enzymes such as cathepsin B, S, and L have been implicated in the progression and metastasis of various malignancies. However, their specific involvement in BC, particularly regarding subtype distinctions such as HER-2 or estrogen receptor (ER) status, remains unclear. Clarifying these associations could significantly enhance our understanding of BC pathophysiology and inform therapeutic strategies. Therefore, we conducted a Mendelian randomization (MR) study to investigate causal relationships between genetically predicted levels of nine cathepsins (H, E, F, B, L2, O, G, S, and Z) and BC risk across multiple subtypes.&lt;/p&gt;&lt;p&gt;We used publicly available genome-wide association study (GWAS) datasets to derive robust genetic instruments. Genetic variants strongly associated with circulating cathepsins levels were extracted from the INTERVAL study (&lt;i&gt;n&lt;/i&gt; = 3301), while BC outcome data were obtained from the FinnGen database (15,680 cases; 167,189 controls) and the Breast Cancer Association Consortium (BCAC) GWAS database, enabling subtype-specific analyses (HER-2 positive, HER-2 negative, ER-positive [ER+], and ER-negative [ER−] cases). We selected instrumental variables using rigorous criteria, including a genome-wide significance threshold (&lt;i&gt;p&lt;/i&gt; &lt; 5 × 10&lt;sup&gt;−6&lt;/sup&gt;) and an &lt;i&gt;F&lt;/i&gt;-statistic &gt; 10 to reduce weak instrument bias. We then performed fixed-effects inverse-variance weighted (IVW) analyses, complemented by MR-Egger, weighted median, and mode-based approaches to confirm robustness. Horizontal pleiotropy was carefully evaluated using MR-Egger intercept and MR-PRESSO tests, ensuring reliability. Reverse MR analysis was conducted to evaluate potential reverse causality by treating BC as the exposure and cathepsins as outcomes. Additionally, multivariable MR accounted for potential interactions among cathepsins, refining causal estimates specific to BC subtypes. Analyses were performed using the “MendelianRandomization” package. The detailed methods were described in Supporting Information S1.&lt;/p&gt;&lt;p&gt;Survival analyses based on cathepsin E (CTSE) expression levels were conducted using data from The Cancer Genome Atlas (TCGA) to further validate findings. Additionally, four human BC cell lines (SKB","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"4 3","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cathepsin B-Responsive Dendronized-Hyaluronic Acid Nanomedicine for Simultaneous Cancer Theranostics","authors":"Chunhua Guo,&nbsp;Yujun Zeng,&nbsp;Yuan Ou,&nbsp;Zhongwei Gu,&nbsp;Kui Luo","doi":"10.1002/mog2.70035","DOIUrl":"https://doi.org/10.1002/mog2.70035","url":null,"abstract":"<p>Tumor microenvironment-responsive imaging-guided therapy has emerged as a novel approach for malignant tumor prognosis and therapy. A multifunctional nanoscale drug delivery system is often employed to realize diagnosis, treatment, monitoring, and evaluation by combining a therapeutic unit and an imaging unit to enable. In this study, we designed and prepared a theranostic nanomedicine by conjugating a small-molecular gadolinium chelate (Diethylenetriaminepentaacetic acid Gadolinium[III] chelate, Gd-DOTA) and a chemotherapeutic drug paclitaxel (PTX) via a cathepsin B-responsive linker (glycylphenylalanylleucylglycine, Gly-Phe-Leu-Gly, GFLG) onto a peptide dendron-hyaluronic acid (HA) hybrid. Upon reaching the tumor microenvironment, the GFLG linker was cleaved by overexpressed cathepsin B, leading to simultaneous release of PTX for targeted chemotherapy and Gd-DOTA for enhanced magnetic resonance imaging (MRI). The experiments demonstrated that the theranostic nanomedicine significantly enhanced MRI contrast and exhibited superior antitumor efficacy in 4T1 breast tumor models without pronounced systemic toxicity. Importantly, under the tumor microenvironment, effective release and clearance of Gd-DOTA from the hybrid postimaging reduced the risk of long-term toxicity. This study presents a feasible approach for cancer theranostics by integrating precise imaging, targeted therapy, and rapid clearance of toxic drugs in a single platform. This promising nanomedicine could be explored for clinical translation.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"4 3","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria ATP Pro-Ferroptosis by Adjusting the Conversion of PUFA to PUFA-PLs","authors":"Chaoyi Xia,&nbsp;Lianchao Gao,&nbsp;Jingshu Min,&nbsp;Caiyun Fu","doi":"10.1002/mog2.70038","DOIUrl":"https://doi.org/10.1002/mog2.70038","url":null,"abstract":"<p>Ferroptosis is a form of iron-dependent regulated necrosis characterized by the abnormal accumulation of peroxidized phospholipids containing polyunsaturated fatty acids (PUFA-PLs). The conversion of PUFA to PUFA-CoA is critical for the synthesis of PUFA-PLs and is reliant on ATP, yet the role of mitochondrial ATP production in regulating ferroptosis remains unclear. In this study, we employed a metabolite deprivation and replenishment system coupled with flow cytometry to investigate the interplay between glutamine metabolism, mitochondrial ATP, and ferroptosis. We demonstrated that depriving cells of glutamine increases intracellular levels of reactive oxygen species (ROS), while also unexpectedly inhibiting ferroptosis induced by cystine deprivation. Mechanistically, glutamine deficiency impaired mitochondrial ATP production, and pharmacological inhibition of mitochondrial ATP export to the cytosol effectively blocked ferroptosis. Further analysis revealed that mitochondrial ATP depletion under glutamine-deficient conditions hindered the conversion of PUFAs to PUFA-CoA, thereby limiting PUFA-PL synthesis and ferroptosis execution. Notably, although glutamine deprivation alone did not directly trigger ferroptosis, it promoted PUFA oxidation and prostaglandin-endoperoxide synthase 2 (PTGS2) expression via ROS accumulation. Together, our findings highlight the critical role of mitochondrial ATP in ferroptosis regulation and provide new insights into the metabolic control of cell death pathways.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using Period Analysis to Timely Provide Serial Data on Long-Term Survival for Gastric Cancer Patients From Taizhou, Eastern China","authors":"Wei Gu,&nbsp;Liangyou Wang,&nbsp;Yongran Cheng,&nbsp;Tianhui Chen,&nbsp;Jinfei Chen","doi":"10.1002/mog2.70031","DOIUrl":"https://doi.org/10.1002/mog2.70031","url":null,"abstract":"<p>Gastric cancer, the fifth most common cancer worldwide, is particularly heavy in China, accounting for 39.5% of global deaths, reported by the International Agency for Research on Cancer (IARC). While timely evaluation of long-term survival of gastric cancer is crucial for guiding early detection screening programs, data on long-term relative survival (RS) for gastric cancer are scarce in China. Traditional methods for estimating 5-year RS require complete 5-year follow-up data, leading to delays of at least 5 years for survival estimates—a challenge that similarly affects 10-, 15-, and 20-year RS. The period analysis approach, introduced by Brenner, overcomes this limitation by enabling more current survival estimates without requiring complete follow-up data [<span>1</span>]. This method is considered the “gold standard” for assessing cancer survival using data from population-based registry and is widely applied in Western countries. In the current study, we aimed to provide, using period analysis, the most recent serial data on long-term survival for gastric cancer patients from a Chinese population, including 5-, 10-, 15-, and 20-year RS.</p><p>Our data came from four high-quality cancer registries in Taizhou City, ranked fifth in population size in Zhejiang Province, China. These registries were selected based on the criterion that death certificate-only (DCO) cases should account for less than 13%, as recommended by Brenner [<span>1</span>], which there were nine registries included initially, to ensure data reliability. Aligned with the International Classification of Diseases (ICD), flowchart of gastric cancer patients included in the analyses was shown in Figure 1A. Eventually, we include the following cases for further analyses, that is, 12,270 cases during 2004–2023 for 20-year RS, 10,515 cases (2009–2023) for 15-year RS, 7427 cases (2014–2023) for 10-year RS, and 3534 cases (2019–2023) for 5-year RS. Period analysis was used to estimate age-adjusted 5-, 10-, 15-, and 20-year RS, stratified by gender, region, and age at diagnosis. RS for patients was calculated as the ratio of observed survival divided by the expected survival based on the life tables using the Ederer II method. All survival estimates were age-adjusted RS using world population standardization for age weights. More details on data analyses are provided in the Supplementary Information S1.</p><p>The basic characteristics of gastric cancer patients were shown in Figure 1B. Approximately 69.0% of patients were males for all four intervals. Furthermore, the majority of cases stood in ≥ 45 years group (approximately 96%), and patients ≥ 65 years accounted for more than half of all gastric patients during all four intervals. As shown in Figure 1C, the most up-to-date estimates of serial data on long-term survival for gastric cancer patients from Taizhou, eastern China, reaching 58.59% for 5-year RS during 2019–2023, 53.04% for 10-years (2014–2023), 46.93% for 15-year RS ","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.70031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}