International Journal of Biological Sciences最新文献

{"title":"Activated AXL Ameliorates Alcohol-associated Steatotic Liver Ischemia-Reperfusion Injury by Inhibiting ER stress and Mitochondria-associated Apoptosis.","authors":"Qi Fang, Qi Yan, Xingyun Liu, Xiaolu Zhang, Lixia Zha, Ruixin Zhang, Zhixin Gao, Jian Du, Lijian Chen","doi":"10.7150/ijbs.103789","DOIUrl":"10.7150/ijbs.103789","url":null,"abstract":"<p><p>Hepatic ischemia-reperfusion (I/R) injury can cause poor prognosis of liver transplantation and hepatectomy, especially in patients with alcohol-associated liver disease (ALD). Apoptosis is closely related to different stages of liver injury, and the death of hepatocytes caused by endoplasmic reticulum (ER) and mitochondria homeostasis perturbation may be key to liver injury. The receptor tyrosine kinases AXL encoded by the gene axl, is a member of the TAM (TYRO3, AXL, and MERTK) family, which participates in various biological processes by binding to the ligand of growth arrest-specific protein 6 (Gas6). However, whether AXL is involved in apoptosis pathways, and the detailed mechanism in hepatic I/R injury remains unknown. In the present study, we found that total AXL is up-regulated while phosphorylated AXL (p-AXL, the active form of AXL) was down-regulated after I/R in human liver tissues from liver transplantation. Consistently, total AXL was found up-regulated while p-AXL was down-regulated during hepatic I/R injury in mice. Pretreatment with Gas6 increased p-AXL expression, reduced ER stress-associated cell apoptosis, alleviated liver damage, and restored ER and mitochondria ultrastructure during hepatic I/R in mice. Furthermore, the ALD model was established by chronic-plus-binge ethanol feeding to explore the role of AXL in I/R liver injury with ethanol-associated steatosis. We found that ALD mice had a lower p-AXL level and were more susceptible to hepatic I/R injury. Importantly, activated AXL ameliorated liver injury by inhibiting IRE1 and PERK pathway to reduce ER stress-associated apoptosis. In conclusion, activated AXL protects alcohol-associated steatotic liver against I/R injury by inhibiting ER stress and mitochondria-associated apoptosis, suggesting that targeting AXL serves as a potential strategy for liver I/R injury, particularly for marginal liver donors with alcohol-associated steatosis.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1294-1307"},"PeriodicalIF":8.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal <i>miR-375-3p</i> mediated lipid metabolism, ferritinophagy and CoQ-dependent pathway contributes to the ferroptosis of keratinocyte in SJS/TEN.","authors":"Chen Zhang, Pei Qiao, ChunYing Xiao, ZiPeng Cao, JiaoLing Chen, Hui Fang, JianKang Yang, ZeHua Kang, ErLe Dang, Shuai Shao, BingYu Pang, QingYang Li, ZhenLai Zhu, ShengXian Shen, Akito Hasegawa, Riichiro Abe, HongJiang Qiao, Gang Wang, Meng Fu","doi":"10.7150/ijbs.98592","DOIUrl":"10.7150/ijbs.98592","url":null,"abstract":"<p><p>Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) manifest life-threatening cutaneous adverse drug reactions characterized by keratinocyte death. Previous studies have indicated that apoptosis and necroptosis are implicated in SJS/TEN pathogeneses. However, other forms of cell death involved in this process remain unidentified. Ferroptosis, cell death driven by iron-dependent lipid peroxidation, has been implicated in various human diseases. In this study, the identification of ferroptosis and the potential effects of ferroptosis on SJS/TEN were investigated. We demonstrated that the skin lesions and plasma of SJS/TEN patients show increased levels of lipid peroxidation and iron. The biomarkers of ferroptosis correlated positively with the disease severity in SJS/TEN patients. Besides, plasma exosomes derived from patients with SJS/TEN exhibited elevated levels of cellular oxidized polyunsaturated fatty acids (PUFAs) and phospholipids phosphatidylethanolamine (PE), the key phospholipids that drive cells towards ferroptotic death. <i>miR-375-3p</i>, enriched in plasma-derived exosomes from SJS/TEN patients, was observed reduce both ferritin heavy chain 1 (FTH1) and ferroptosis suppressor protein 1 (FSP1) expression. Parallelly, exosomal <i>miR-375-3p</i> overexpression increased the level of lipid peroxidation but decreased the coenzyme Q10 (CoQ10), thus enhancing the ferroptosis rate of keratinocyte. Above all, we concluded that ferritinophagy-mediated ferroptosis, lipid metabolism, and the FSP1-CoQ-dependent pathway in ferroptosis are critical mechanisms contributing to SJS/TEN. Targeting ferroptosis in keratinocyte may be a therapeutic strategy for preventing SJS/TEN in the future.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1275-1293"},"PeriodicalIF":8.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM32 promotes neuronal ferroptosis by enhancing K63-linked ubiquitination and subsequent p62-selective autophagic degradation of GPX4.","authors":"Xin Zhou, Yuqing Zhao, Shixue Huang, Haoming Shu, Yinuo Zhang, Haiyuan Yang, Yilong Ren, Xuhui Zhou, Wei Liu, Tengfei Song, Jianquan Zhao, Jun Ma","doi":"10.7150/ijbs.106690","DOIUrl":"10.7150/ijbs.106690","url":null,"abstract":"<p><p>Ferroptosis, characterized by iron-dependent phospholipid peroxidation, is recognized as one of the cell death pathways activated following spinal cord injury (SCI). However, the precise regulatory mechanisms governing this process remain poorly understood. Here, this study identified TRIM32, an E3 ubiquitin ligase, as a key enhancer of neuronal ferroptosis. TRIM32 promoted neuronal ferroptosis by accelerating the degradation of GPX4, which is an essential inhibitor of ferroptosis. Conditional deletion of <i>Trim32</i> in neurons markedly inhibited neuronal ferroptosis and promoted neuronal survival, eventually improving mouse locomotor functional recovery after SCI. However, overexpression of <i>Trim32</i> showed aggravated neuronal loss and poor behavioral function, which could be attenuated by ferroptosis inhibitor Liproxstatin-1. Mechanistically, TRIM32 interacted with GPX4, promoted K63-linked ubiquitination modification of GPX4 at K107, thus enhanced p62-dependent autophagic degradation of GPX4. Moreover, ROS-ATM-Chk2 signaling pathway phosphorylates TRIM32 at S55, further contributing to GPX4 ubiquitination and degradation and subsequent neuronal ferroptosis after SCI, suggesting a positive feedback loop between ROS and TRIM32. Clinically, lipid peroxidation was significantly promoted in patients with SCI. These findings reveal that TRIM32 functions as a neuronal ferroptosis enhancer which is detrimental to neuronal survival and locomotor functional recovery in mice after SCI by promoting K63-linked ubiquitination and subsequent p62-dependent autophagic degradation of GPX4, suggesting a promising therapeutic target for SCI.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1259-1274"},"PeriodicalIF":8.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DDX17-Mediated Upregulation of CXCL8 Promotes Hepatocellular Carcinoma Progression <i>via</i> Co-activating β-catenin/NF-κB Complex.","authors":"Hui Liu, Xiaoliang Gao, Wenyao Zhang, Xin Fu, Jing Zhang, Qiangqiang Yuan, Jing Jin, Xinyu Du, Renlong Li, Yan Li, Jun Yu, Qiujin Zhang, Xianchun Gao, Liang Zhang, Yuwei Ling, Jing Wu, Lin Wang, Jinliang Xing, Fulin Chen, Yongzhan Nie","doi":"10.7150/ijbs.104165","DOIUrl":"10.7150/ijbs.104165","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a well-known inflammation-related cancer, that accounts for fifth most prevalent neoplasm and the third major driver of cancer associated fatality globally. Accumulating evidence has elucidated that C-X-C motif chemokine ligands (CXCLs) are aberrantly upregulated in HCC and are involved in inflammation-induced hepatocarcinogenesis and metastasis. Herein, we identified a novel function of DEAD-box RNA helicase 17 (DDX17) as an oncogenic factor via transactivating CXCL8 in HCC. Unlike the adjacent nontumor tissues, DDX17 was highly expressed in tumor tissues compared in two independent cohorts and that it acts as an independent prognostic indicator for patients who have HCC. Mechanistically, DDX17 interacts with β-catenin and NF-κB, and promotes their nuclear translocation to promote the transcription of the inflammatory gene CXCL8, thus promoting HCC proliferation and invasion <i>in vitro</i> and <i>in vivo</i>. More interestingly, stimulation with recombinant human CXCL8 augmented the interaction of NF-κB with DDX17/β-catenin and enhanced its autocrine activation by promoting the phosphorylation of IκBα. Furthermore, blocking the association of the DDX17/β-catenin/NF-κB complex with a CXCR1/2 inhibitor markedly abrogated DDX17-mediated HCC proliferation and metastasis. Overall, this study provided new insights into DDX17-mediated pro-inflammatory chemokine activation, which unveiled the association between DDX17 and β-catenin/ NF-κB complex in transactivating the expression of CXCL8. The usage of CXCR1/2 inhibitor to block DDX17-induced CXCL8 signaling activation might be a potential therapeutic approach for HCC treatment.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1342-1360"},"PeriodicalIF":8.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Updated review of research on the role of the gut microbiota and microbiota-derived metabolites in acute pancreatitis progression and inflammation-targeted therapy.","authors":"Qiang Liu, Kaiyi Ruan, Zihui An, Lingyun Li, Cong Ding, Dongchao Xu, Jianfeng Yang, Xiaofeng Zhang","doi":"10.7150/ijbs.108858","DOIUrl":"10.7150/ijbs.108858","url":null,"abstract":"<p><p>Acute pancreatitis (AP) is characterized by autodigestion of the pancreas, and some patients may rapidly progress to systemic inflammation, pancreatic necrosis, and multi-organ failure. Numerous studies have detailed the bidirectional communication networks between the pancreas and the intestinal microbiota, as well as its metabolites. Such crosstalk affects the progression of AP and recovery through intestinal barrier disruption. Furthermore, advances in experimental research and clinical studies have indicated that gut microorganisms exhibit distinct alterations in response to different levels of severity and etiologies of AP. This information has greatly expanded our knowledge of the role of the gut microflora and microbial metabolites in the pathology of disease and has reinforced the basis of therapeutic approaches that target candidate intestinal microbiota. In this review, we aim to provide an overview of the composition and diversity of the gut microbial community, to highlight the candidate bacteria and microbiota-derived metabolites responsible for AP, and to elucidate their interactions with and regulation of immune-relevant receptors in intestinal epithelial cells (IECs) in the host. Future research should focus on identifying and characterizing AP-associated bacterial strains, elucidating their distinct pathogenic mechanisms across different etiologies and stages of AP, and leveraging these insights to develop preventive and therapeutic strategies.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1242-1258"},"PeriodicalIF":8.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting ferroptosis to enhance the efficacy of mesenchymal stem cell-based treatments for intervertebral disc degeneration.","authors":"Yuzhu Xu, Xuanfei Xu, Renjie Chai, Xiaotao Wu","doi":"10.7150/ijbs.107021","DOIUrl":"10.7150/ijbs.107021","url":null,"abstract":"<p><p>Although mesenchymal stromal cell (MSC) implantation shows promise for repairing intervertebral disc (IVD) degeneration (IVDD), their limited retention within degenerative IVDs compromises therapeutic efficacy. The oxidative stress in the microenvironment of degenerated IVDs induces a surge in reactive oxygen species production within MSCs, disrupting the balance between oxidation and antioxidation, and ultimately inducing ferroptosis. Recent evidence has suggested that targeting ferroptosis in MSCs could enhance MSC retention, extend the survival of transplanted MSCs, and markedly delay the pathological progression of IVDD. By targeting ferroptosis, a novel approach emerges to boost the efficacy of MSC transplantation therapy for IVDD. In this review, current research on targeting ferroptosis in MSCs is discussed from various perspectives, including the targeting of specific genes and pathways, drug preconditioning, and hydrogel encapsulation. A detailed discussion on the effects of targeting ferroptosis in MSCs on the transplantation repair of degenerated IVDs is provided. Insights that could guide improvements in stem cell transplantation therapies are also offered. Significantly, this review presents specific ideas for our future foundational research. These insights outline promising avenues for future clinical translation and will contribute to developing and optimizing treatment strategies for MSC transplantation therapy, maximizing benefits for patients with lumbar IVDD.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1222-1241"},"PeriodicalIF":8.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SERINC2-mediated serine metabolism promotes cervical cancer progression and drives T cell exhaustion.","authors":"Yixuan Sun, Yang Zhou, Qihua Peng, Wanzhen Zhou, Xiao Li, Ruiwen Wang, Yifan Yin, Huixian Huang, Hongfei Yao, Qing Li, Xueli Zhang, Lipeng Hu, Shuheng Jiang, Zhigang Zhang, Dongxue Li, Xiaolu Zhu, Yincheng Teng","doi":"10.7150/ijbs.105572","DOIUrl":"10.7150/ijbs.105572","url":null,"abstract":"<p><p>Cervical cancer remains the most prevalent gynecological malignant disease. Reprogramming tumor immune metabolism stands out as a novel promising therapeutic target. Here, we identified serine incorporator 2 (SERINC2) as a critical gene which highly expressed in cervical cancer and negatively correlated with clinical outcomes. Through functional assays, SERINC2 was determined to play a pro-tumoral role both <i>in vivo</i> and <i>in vitro</i>. Besides, the growth of cervical cancer cells was found to be largely dependent on serine in a manner influenced by SERINC2. As a serine transport associated protein, SERINC2 knockdown significantly reduced cervical cancer cells' intracellular serine level and altered the serine-associated-lipid metabolism. Immune infiltration analysis revealed that SERINC2 was negatively associated with CD8⁺ T cell infiltration and function. More importantly, we demonstrated a competitive relation between cancer cells and immune cells brought about by SERINC2. Mechanistically, cancer cells SERINC2 preferentially competed for micro-environmental serine over CD8⁺ T cells and rendered T cell exhaustion. Overall, SERINC2 remodels cancer development and serine metabolism in the tumor immune microenvironment (TIME), establishing an immunosuppressive and pro-tumoral milieu.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1361-1377"},"PeriodicalIF":8.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancement Opportunities and Endeavor of Innovative Targeted Therapies for Small Cell Lung Cancer.","authors":"Wei Ouyang, Ziyao Xu, Shaoyu Guan, Yang Hu, Xiaoxue Gou, Zhe Liu, Wei Guo, Ye Huang, Lifen Zhang, Xingmei Zhang, Tian Li, Bin Yang","doi":"10.7150/ijbs.105973","DOIUrl":"10.7150/ijbs.105973","url":null,"abstract":"<p><p>Small cell lung cancer (SCLC) is an intractable disease with rapid progression and high mortality, presenting a persistent obstacle impeding clinical management. Although recent advancements in immunotherapy have enhanced the response rates of platinum-based chemotherapy regimens, the emergence of acquired resistance invariably leads to recurrence and metastasis. Consequently, there is an urgent necessity to explore novel therapeutic targets and optimize existing treatment strategies. This article comprehensively reviews the currently available therapeutic modalities for SCLC. It delves into the immunologic prognostic implications by analyzing selected immune-related signatures. Moreover, it conducts an in-depth exploration of the molecular subtyping of SCLC and the associated molecular pathways to identify potential therapeutic targets. Specifically, the focus is on clinical interventions targeting delta-like ligand 3 (DLL3), elucidating its resistance mechanisms and demonstrating its notable antitumor efficacy. Furthermore, the study examines the mechanisms of chimeric antigen receptor (CAR) T and antibody-drug conjugate (ADC), covering resistance issues and strategies for optimizing resistance management, with particular emphasis being placed on analyzing the prospects and clinical value of CAR T therapy in the context of SCLC. Moreover, the effectiveness of poly ADP-ribose polymerase and ataxia telangiectasia and rad3/checkpoint kinase 1 inhibitors is discussed and underscores the advantages of combining these inhibitors with standard chemotherapy to combat chemoresistance and enhance the antitumor effects of immunotherapies. Overall, this study investigates emerging strategies for targeted therapies and optimized combination regimens to overcome resistance in SCLC and highlights future strategies for new therapeutic technologies for SCLC.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1322-1341"},"PeriodicalIF":8.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Downregulation of PGAM2 alleviates angiotensin II-induced cardiac hypertrophy by destabilizing HSP90 and inactivating the mTOR/IKKα signaling pathway.","authors":"Ying Li, Wen-Jing Li, Jia-Min Du, Hui-Hui Wu, Si-Yuan Zhou, Min Li, Yue-Yan Li, Shu-Ya Wang, Hui-Yun Wang, Yan Zheng, Qun-Ye Zhang, Li-Ming Li, Fan-Liang Meng, Guo-Hai Su","doi":"10.7150/ijbs.102251","DOIUrl":"10.7150/ijbs.102251","url":null,"abstract":"<p><p>Pathological cardiac hypertrophy is a major contributor to heart failure. The present study aims to elucidate the role and mechanisms of phosphoglycerate mutase 2 (PGAM2) in the pathogenesis of cardiac hypertrophy. PGAM2 expression was increased in both primary neonatal rat ventricular myocytes (NRVMs) and rat models in response to angiotensin II (Ang II). Downregulation of PGAM2 alleviated cardiac hypertrophy. Mechanistically, we found PGAM2 directly interacts with HSP90 through residues 319-323 and 622-629 in the middle and carboxy-terminal domain of HSP90 respectively. This interaction was further enhanced under Ang II stimulation. Additionally, in the presence of PGAM2, it competed with E3 ubiquitin ligase SYVN1 to interact with HSP90, effectively inhibiting the ubiquitination and degradation of HSP90. Therefore, deficiency of PGAM2 results in the downregulation of the HSP90 and its downstream mTOR and client protein IKKα signaling pathway, both of which play crucial roles in the progression of cardiac hypertrophy. <i>In vivo</i>, we further confirmed that PGAM2 knockdown alleviated cardiac hypertrophy through downregulation of HSP90 and mTOR/IKKα signaling pathway. Taken together, we first demonstrated that downregulation of PGAM2 alleviates cardiac hypertrophy induced by Ang II, which provides a novel target for the treatment of myocardial hypertrophy and heart failure.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1308-1321"},"PeriodicalIF":8.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-associated macrophages drive heterogenetic CD10^High cancer stem cells to implement tumor-associated neutrophils reprogramming in oral squamous cell carcinoma.","authors":"Yuanhe You, Zhong Du, Zhuowei Tian, Shunshun Li, Fan Yu, Meng Xiao, Yue He, Yanan Wang","doi":"10.7150/ijbs.100611","DOIUrl":"10.7150/ijbs.100611","url":null,"abstract":"<p><p>Tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) widely participate in the malignant progression in cancer. Previously, we have demonstrated that M1-like TAMs cascaded a stem-like phenotype of oral squamous cell carcinoma (OSCC). Yet, the underlying mechanisms still need to be demonstrated for the regulation of TAMs on cancer stem cells (CSCs) in OSCC. In this study, we investigated a group of CSCs with increased expression of cluster differentiation 10 (CD10), which acted as a mediator in the interaction network between TAMs and tumor-associated neutrophils (TANs) in OSCC. The results showed a significant association between TAMs infiltrations and increased expression of CD10 among all the CSCs-related molecules in OSCC. Then, we validated that OSCC cells with high CD10 expression possessed increased CSCs characteristics. TAMs could drive the heterogenetic CD10^High CSCs by activating the IL6/STAT3/CD10 pathway. Furthermore, CD10^High CSCs could recruit and reprogram tumor-associated neutrophils (TANs) in an immunosuppressive state by secreting S100A8/A9 in OSCC. These finding indicated that CD10^High CSCs played great roles in signaling crosstalk between TAMs and TANs in OSCC, by which infiltrated TAMs drive CD 10^High CSCs to recruit and reprogram TANs in an immunosuppressive state. Herein, we managed to demonstrate that TAMs could directly regulate a heterogenetic cluster of CSCs with high CD10 expression, and CD10^High CSCs could recruit and reprogram TANs in OSCC. The novel crosstalk among OSCC-TAMs-CD10^High CSCs-TANs might bring new prospects for improving the treatment strategies for OSCC patients.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1110-1126"},"PeriodicalIF":8.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}