Apoptosis最新文献

{"title":"Ferroptosis crosstalk in anti-tumor immunotherapy: molecular mechanisms, tumor microenvironment, application prospects","authors":"Yining Lu,&nbsp;Xiaoting Xie,&nbsp;Lianxiang Luo","doi":"10.1007/s10495-024-01997-8","DOIUrl":"10.1007/s10495-024-01997-8","url":null,"abstract":"<div><p>Immunotherapies for cancer, specifically immune checkpoint inhibition (ICI), have shown potential in reactivating the body’s immune response against tumors. However, there are challenges to overcome in addressing drug resistance and improving the effectiveness of these treatments. Recent research has highlighted the relationship between ferroptosis and the immune system within immune cells and the tumor microenvironment (TME), suggesting that combining targeted ferroptosis with immunotherapy could enhance anti-tumor effects. This review explores the potential of using immunotherapy to target ferroptosis either alone or in conjunction with other therapies like immune checkpoint blockade (ICB) therapy, radiotherapy, and nanomedicine synergistic treatments. It also delves into the roles of different immune cell types in promoting anti-tumor immune responses through ferroptosis. Together, these findings provide a comprehensive understanding of synergistic immunotherapy focused on ferroptosis and offer innovative strategies for cancer treatment.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 11-12","pages":"1914 - 1943"},"PeriodicalIF":6.1,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SNCA is a potential therapeutic target for COVID-19 infection in diffuse large B-cell lymphoma patients","authors":"Can Chen,&nbsp;Yun Li,&nbsp;Yiwei Li,&nbsp;Zhenzhen Chen,&nbsp;Pengfei Shi,&nbsp;Yaping Xie,&nbsp;Shenxian Qian","doi":"10.1007/s10495-024-01996-9","DOIUrl":"10.1007/s10495-024-01996-9","url":null,"abstract":"<div><p>Cuprotosis related genes (CRGs) have been proved to be potential therapeutic targets for coronavirus disease 2019 (COVID-19) and cancer, but their immune and molecular mechanisms in COVID-19 infection in Diffuse Large B-cell Lymphoma (DLBC/DLBCL) patients are rarely reported. Our research goal is first to screen the key CRGs in COVID-19 through univariate analysis, machine learning and clinical samples. Secondly, we determined the expression and prognostic role of key CRGs in DLBCL through pan-cancer analysis. We validated the expression levels and prognosis using multiple datasets and independent clinical samples and validated the functional role of key CRGs in DLBCL through cell experiments. Finally, we validated the expression levels of CRGs in COVID-19 infected DLBCL patients samples and analyzed their common pathways in COVID-19 and DLBCL. The results show that synuclein-alpha (SNCA) is the common key differential gene of COVID-19 and DLBCL. DLBCL cells confirm that high expression of SNCA can significantly promote cell apoptosis and significantly inhibit the cycle progression of DLBCL. High expression of SNCA can regulate the binding of major histocompatibility complexes (MHCs) and T cell receptor (TCR) by regulating immune infiltration of Dendritic cells, effectively enhancing T cell-mediated anti-tumor immunity and clearing cancer cells. In conclusion, SNCA may be a potential therapeutic target for COVID-19 infection in DLBCL patients. Our study provides a theoretical basis for improving the clinical treatment of COVID-19 infection in DLBCL patients.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 9-10","pages":"1454 - 1465"},"PeriodicalIF":6.1,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615816","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":"The role of hydrogen sulfide regulation of ferroptosis in different diseases","authors":"Jingwen Lian,&nbsp;Yuhang Chen,&nbsp;Yanting Zhang,&nbsp;Shiyun Guo,&nbsp;Honggang Wang","doi":"10.1007/s10495-024-01992-z","DOIUrl":"10.1007/s10495-024-01992-z","url":null,"abstract":"<div><p>Ferroptosis is a programmed cell death that relies on iron and lipid peroxidation. It differs from other forms of programmed cell death such as necrosis, apoptosis and autophagy. More and more evidence indicates that ferroptosis participates in many types of diseases, such as neurodegenerative diseases, ischemia-reperfusion injury, cardiovascular diseases and so on. Hence, clarifying the role and mechanism of ferroptosis in diseases is of great significance for further understanding the pathogenesis and treatment of some diseases. Hydrogen sulfide (H₂S) is a colorless and flammable gas with the smell of rotten eggs. Many years ago, H₂S was considered as a toxic gas. however, in recent years, increasing evidence indicates that it is the third important gas signaling molecule after nitric oxide and carbon monoxide. H₂S has various physiological and pathological functions such as antioxidant stress, anti-inflammatory, anti-apoptotic and anti-tumor, and can participate in various diseases. It has been reported that H₂S regulation of ferroptosis plays an important role in many types of diseases, however, the related mechanisms are not fully clear. In this review, we reviewed the recent literature about the role of H₂S regulation of ferroptosis in diseases, and analyzed the relevant mechanisms, hoping to provide references for future in-depth researches.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 9-10","pages":"1377 - 1392"},"PeriodicalIF":6.1,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted delivery of FAK siRNA by engineered exosomes to reverse cetuximab resistance via activating paraptosis in colon cancer","authors":"Yiting Geng,&nbsp;Wei Xia,&nbsp;Xiao Zheng,&nbsp;Lujun Chen,&nbsp;You Zhou,&nbsp;Jun Feng,&nbsp;Ye Yuan,&nbsp;Mingyue Zhang,&nbsp;Jianwen Lu,&nbsp;Shanshan Wei,&nbsp;Wenwei Hu","doi":"10.1007/s10495-024-01986-x","DOIUrl":"10.1007/s10495-024-01986-x","url":null,"abstract":"<div><h3>Background</h3><p>Cetuximab is extensively used in the treatment of metastatic colorectal cancer (mCRC). However, resistance poses a significant challenge to successful therapy. Recently, paraptosis, a non-classical programmed cell death, has garnered increased attention for its potential application value in antitumor treatments. We aimed to identify the essential pathways and signaling molecules involved in paraptosis inhibition and select them as therapeutic targets in cetuximab resistance. Additionally, engineered exosome technology is used as a drug delivery system with both targeted and effector properties.</p><h3>Results</h3><p>By comparing the differential expression of paraptosis-related genes between drug-resistant colon cancer cells and sensitive cells, it was observed that the paraptosis level induced by cetuximab was significantly downregulated in drug-resistant cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified the focal adhesion kinase (FAK) signaling pathway as a key pathway involved in the suppression of paraptosis. The biological function of FAK in cetuximab-resistant cells was investigated through cell morphology observation, CCK-8 assay, colony formation assay, RT-qPCR, Western Blot, and loss-of-function experiments. The results showed that the FAK signaling pathway was significantly upregulated in cetuximab-resistant colon cancer cells, and siRNA interference targeting FAK could notably inhibit cell proliferation while upregulating the paraptosis level. Based on this, engineered colon cancer cells targeted and FAK siRNA loaded exosomes (CT-Exo-siFAK1) were constructed. In vitro experiments, CT-Exo-siFAK1 could effectively activate paraptosis and inhibit the proliferation of drug-resistant colon cancer cells. In vivo experiments also confirmed that CT-Exo-siFAK1 significantly suppressed tumor growth and metastasis while upregulating the paraptosis level.</p><h3>Conclusion</h3><p>This study suggests that FAK signaling pathway-mediated inhibition of paraptosis levels is crucial in the sensitivity of cetuximab targeted therapy in colon cancer, and the use of engineered exosomes to deliver FAK siRNA may be an effective strategy to reverse cetuximab resistance.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 11-12","pages":"1959 - 1977"},"PeriodicalIF":6.1,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496877","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":"Disulfidptosis: A new type of cell death","authors":"Fei Xiao,&nbsp;Hui-Li Li,&nbsp;Bei Yang,&nbsp;Hao Che,&nbsp;Fei Xu,&nbsp;Gang Li,&nbsp;Cheng-Hui Zhou,&nbsp;Sheng Wang","doi":"10.1007/s10495-024-01989-8","DOIUrl":"10.1007/s10495-024-01989-8","url":null,"abstract":"<div><p>Disulfidptosis is a novel form of cell death that is distinguishable from established programmed cell death pathways such as apoptosis, pyroptosis, autophagy, ferroptosis, and oxeiptosis. This process is characterized by the rapid depletion of nicotinamide adenine dinucleotide phosphate (NADPH) in cells and high expression of solute carrier family 7 member 11 (SLC7A11) during glucose starvation, resulting in abnormal cystine accumulation, which subsequently induces andabnormal disulfide bond formation in actin cytoskeleton proteins, culminating in actin network collapse and disulfidptosis. This review aimed to summarize the underlying mechanisms, influencing factors, comparisons with traditional cell death pathways, associations with related diseases, application prospects, and future research directions related to disulfidptosis.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 9-10","pages":"1309 - 1329"},"PeriodicalIF":6.1,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417450","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":"The significant mechanism and treatments of cell death in heatstroke","authors":"Zixin Wang,&nbsp;Jie Zhu,&nbsp;Dingshun Zhang,&nbsp;Jinke Lv,&nbsp;Liangping Wu,&nbsp;Zhifeng Liu","doi":"10.1007/s10495-024-01979-w","DOIUrl":"10.1007/s10495-024-01979-w","url":null,"abstract":"<div><p>With global warming, extreme environmental heat is becoming a social issue of concern, which can cause adverse health results including heatstroke (HS). Severe heat stress is characterized by cell death of direct heat damage, excessive inflammatory responses, and coagulation disorders that can lead to multiple organ dysfunction (MODS) and even death. However, the significant pathophysiological mechanism and treatment of HS are still not fully clear. Various modes of cell death, including apoptosis, pyroptosis, ferroptosis, necroptosis and PANoptosis are involved in MODS induced by heatstroke. In this review, we summarized molecular mechanism, key transcriptional regulation as for HSF1, NRF2, NF-κB and PARP-1, and potential therapies of cell death resulting in CNS, liver, intestine, reproductive system and kidney injury induced by heat stress. Understanding the mechanism of cell death provides new targets to protect multi-organ function in HS.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 7-8","pages":"967 - 980"},"PeriodicalIF":6.1,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The landscape of programmed cell death-related lncRNAs in Alzheimer’s disease and Parkinson’s disease","authors":"Ning Zhao,&nbsp;Junyi Wang,&nbsp;Shan Huang,&nbsp;Jingyu Zhang,&nbsp;Jin Bao,&nbsp;Haisen Ni,&nbsp;Xinhang Gao,&nbsp;Chunlong Zhang","doi":"10.1007/s10495-024-01984-z","DOIUrl":"10.1007/s10495-024-01984-z","url":null,"abstract":"<div><p>This study delivers a thorough analysis of long non-coding RNAs (lncRNAs) in regulating programmed cell death (PCD), vital for neurodegenerative diseases like Alzheimer’s disease (AD) and Parkinson’s disease (PD). We propose a new framework PCDLnc, and identified 20 significant lncRNAs, including <i>HEIH</i>, <i>SNHG15</i>, and <i>SNHG5</i>, associated with PCD gene sets, which were known for roles in proliferation and apoptosis in neurodegenerative diseases. By using GREAT software, we identified regulatory functions of top lncRNAs in different neurodegenerative diseases. Moreover, lncRNAs cis-regulated mRNAs linked to neurodegeneration, including <i>JAK2</i>, <i>AKT1</i>, <i>EGFR</i>, <i>CDC42</i>, <i>SNCA</i>, and <i>ADIPOQ</i>, highlighting their therapeutic potential in neurodegenerative diseases. A further exploration into the differential expression of mRNA identified by PCDLnc revealed a role in apoptosis, ferroptosis and autophagy. Additionally, protein-protein interaction (PPI) network analysis exposed abnormal interactions among key genes, despite their consistent expression levels between disease and normal samples. The randomforest model effectively distinguished between disease samples, indicating a high level of accuracy. Shared gene subsets in AD and PD might serve as potential biomarkers, along with disease-specific gene sets. Besides, we also found the strong relationship between AD and immune infiltration. This research highlights the role of lncRNAs and their associated genes in PCD in neurodegenerative diseases, offering potential therapeutic targets and diagnostic markers for future study and clinical application.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 9-10","pages":"1584 - 1599"},"PeriodicalIF":6.1,"publicationDate":"2024-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Mutual Regulatory Role of Ferroptosis and Immunotherapy in Anti-tumor Therapy","authors":"Zhiguo Mao,&nbsp;Yilong Hu,&nbsp;Yinan Zhao,&nbsp;Xiaolei Zhang,&nbsp;Lin Guo,&nbsp;Xiaoran Wang,&nbsp;Jinying Zhang,&nbsp;Mingsan Miao","doi":"10.1007/s10495-024-01988-9","DOIUrl":"10.1007/s10495-024-01988-9","url":null,"abstract":"&lt;div&gt;&lt;p&gt;Ferroptosis is a form of cell death that is triggered by the presence of ferrous ions and is characterized by lipid peroxidation induced by these ions. The mechanism exhibits distinct morphological characteristics compared to apoptosis, autophagy, and necrosis. A notable aspect of ferroptosis is its ability to inhibit uncontrolled tumor replication and immortalization, especially in malignant, drug-resistant, and metastatic tumors. Additionally, immunotherapy, a novel therapeutic approach for tumors, has been found to have a reciprocal regulatory relationship with ferroptosis in the context of anti-tumor therapy. A comprehensive analysis of ferroptosis and immunotherapy in tumor therapy is presented in this paper, highlighting the potential for mutual adjuvant effects. Specifically, we discuss the mechanisms underlying ferroptosis and immunotherapy, emphasizing their ability to improve the tumor immune microenvironment and enhance immunotherapeutic effects. Furthermore, we investigate how immunotherapeutic factors may increase the sensitivity of tumor cells to ferroptosis. We aim to provide a prospective view of the promising value of combined ferroptosis and immunotherapy in anticancer therapy by elucidating the mutual regulatory network between each.&lt;/p&gt;&lt;h3&gt;Graphical Abstract&lt;/h3&gt;&lt;p&gt;Ferroptosis in the tumor microenvironment involves intricate crosstalk between tumor cells and immune cells. Through MHC recognition, CD8&lt;sup&gt;+&lt;/sup&gt;T cells activate the JAK1/STAT1 pathway in tumor cells, impairing the function of System Xc and reducing GSH and GPX4 expression to promote tumor cell ferroptosis. Additionally, activation of the STAT1-IRF1-ACSL4 pathway could also promote ferroptosis. The blockade of the antioxidant pathway in tumor cells induces ferroptosis, and the released DAMPs could promote DCs maturation through the cGAMP-STING-TBK1 pathway, leading to antigen presentation that activates CD8&lt;sup&gt;+&lt;/sup&gt;T cells. The release of DAMPs also induces the M1-type polarization of macrophages, which exerts an anti-tumor effect. The anti-tumor effects of CD8&lt;sup&gt;+&lt;/sup&gt;T cells could also be enhanced by blocking inhibitory immune checkpoints such as PD-1, PD-L1, CTLA4, and LAG3. Abbreviations: ACSL4, acyl-CoA synthetase long-chain family member 4; BH4, tetrahydrobiopterin; cGAMP, cyclic GMP-AMP; CTLA4, cytotoxic T lymphocyte-associated antigen-4; DCs, dendritic cells; DHFR, dihydrofolate reductase; DHODH, dihydroorotate dehydrogenase; GPX4, glutathione peroxidase 4; GSH, glutathione; HIF-1α, Hypoxia-Inducible Factor-1α;IFN-γ, interferon-γ; IRF1, interferon regulatory factor 1;IRP1, iron regulatory protein 1; JAK 1, janus kinase; LAG3, lymphocyte activation gene 3; MHC, major histocompatibility complex; NRF2, nuclear factor erythroid-2-related factor 2; PD-1, programmed death protein -1; PD-L1, programmed death ligand 1; PUFA, polyunsaturated fatty acid; ROS, reative oxygen species; STAT1, signal transducer and activator of transcription 1; STING, st","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 9-10","pages":"1291 - 1308"},"PeriodicalIF":6.1,"publicationDate":"2024-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295499","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 PAX8 sensitizes ovarian cancer cells to ferroptosis by inhibiting glutathione synthesis","authors":"Yanlin Luo,&nbsp;Xiaoli Liu,&nbsp;Yibing Chen,&nbsp;Qing Tang,&nbsp;Chengsi He,&nbsp;Xinyi Ding,&nbsp;Jiachun Hu,&nbsp;Zheyou Cai,&nbsp;Xiang Li,&nbsp;Hailing Qiao,&nbsp;Zhengzhi Zou","doi":"10.1007/s10495-024-01985-y","DOIUrl":"10.1007/s10495-024-01985-y","url":null,"abstract":"<div><p>Ovarian cancer is a malignant tumor originating from the ovary, characterized by its high mortality rate and propensity for recurrence. In some patients, especially those with recurrent cancer, conventional treatments such as surgical resection or standard chemotherapy yield suboptimal results. Consequently, there is an urgent need for novel anti-cancer therapeutic strategies. Ferroptosis is a distinct form of cell death separate from apoptosis. Ferroptosis inducers have demonstrated promising potential in the treatment of ovarian cancer, with evidence indicating their ability to enhance ovarian cancer cell sensitivity to cisplatin. However, resistance of cancer cells to ferroptosis still remains an inevitable challenge. Here, we analyzed genome-scale CRISPR-Cas9 loss-of function screens and identified PAX8 as a ferroptosis resistance protein in ovarian cancer. We identified PAX8 as a susceptibility gene in GPX4-dependent ovarian cancer. Depletion of PAX8 rendered GPX4-dependent ovarian cancer cells significantly more sensitive to GPX4 inhibitors. Additionally, we found that PAX8 inhibited ferroptosis in ovarian cancer cells. Combined treatment with a PAX8 inhibitor and RSL3 suppressed ovarian cancer cell growth, induced ferroptosis, and was validated in a xenograft mouse model. Further exploration of the molecular mechanisms underlying PAX8 inhibition of ferroptosis mutations revealed upregulation of glutamate-cysteine ligase catalytic subunit (GCLC) expression. GCLC mediated the ferroptosis resistance induced by PAX8 in ovarian cancer. In conclusion, our study underscores the pivotal role of PAX8 as a therapeutic target in GPX4-dependent ovarian cancer. The combination of PAX8 inhibitors such as losartan and captopril with ferroptosis inducers represents a promising new approach for ovarian cancer therapy.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 9-10","pages":"1499 - 1514"},"PeriodicalIF":6.1,"publicationDate":"2024-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TNIK in disease: from molecular insights to therapeutic prospects","authors":"Xue Wu,&nbsp;Zhe Zhang,&nbsp;Zhenye Qiu,&nbsp;Xiaopeng Wu,&nbsp;Junmin Chen,&nbsp;Lu Liu,&nbsp;Xiaoyi Liu,&nbsp;Shiyan Zhao,&nbsp;Yang Yang,&nbsp;Ye Zhao","doi":"10.1007/s10495-024-01987-w","DOIUrl":"10.1007/s10495-024-01987-w","url":null,"abstract":"<div><p>TRAF2 and NCK interacting kinase (TNIK), a critical interacting protein kinase, is currently receiving wide attention. TNIK is found in various human body organs and tissues and participates in cell motility, proliferation, and differentiation. On the one hand, its aberrant expression is related to the onset and progression of numerous malignant tumors. On the other hand, TNIK is important in neuronal growth, proliferation, differentiation, and synaptic formation. Thus, the novel therapeutic strategies for targeting TNIK offer a promising direction for cancer, neurological or psychotic disorders. Here, we briefly summarized the biological information of TNIK, reviewed the role and regulatory mechanism in cancer and neuropsychiatric diseases, and introduced the research progress of inhibitors targeting TNIK. Taken together, this review hopes to contribute to the in-depth understanding of the function and regulatory mechanism of TNIK, which is of great significance for revealing the role of TNIK in the occurrence and treatment of diseases.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 9-10","pages":"1361 - 1376"},"PeriodicalIF":6.1,"publicationDate":"2024-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}