Apoptosis最新文献

{"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}

{"title":"FAT10 induces immune suppression by upregulating PD-L1 expression in hepatocellular carcinoma","authors":"Qingbin Wang,&nbsp;Wenliang Tan,&nbsp;Ziyu Zhang,&nbsp;Qiuju Chen,&nbsp;Zhiqin Xie,&nbsp;Lei Yang,&nbsp;Chenwei Tang,&nbsp;Hongkai Zhuang,&nbsp;Bingkun Wang,&nbsp;Jiahao Jiang,&nbsp;Xiaowu Ma,&nbsp;Wentao Wang,&nbsp;Yonglin Hua,&nbsp;Changzhen Shang,&nbsp;Yajin Chen","doi":"10.1007/s10495-024-01982-1","DOIUrl":"10.1007/s10495-024-01982-1","url":null,"abstract":"<div><p>The upregulation of programmed death ligand 1 (PD-L1) plays a crucial role in facilitating cancer cells to evade immune surveillance through immunosuppression. However, the precise regulatory mechanisms of PD-L1 in hepatocellular carcinoma (HCC) remain undefined. The correlation between PD-L1 and ubiquitin-like molecules (UBLs) was studied using sequencing data from 20 HCC patients in our center, combined with TCGA data. Specifically, the association between FAT10 and PD-L1 was further validated at both the protein and mRNA levels in HCC tissues from our center. Subsequently, the effect of FAT10 on tumor progression and immune suppression was examined through both in vivo and in vitro experiments. Utilizing sequencing data, qPCR, and Western blotting assays, we confirmed that FAT10 was highly expressed in HCC tissues and positively correlated with PD-L1 expression. Additionally, in vitro experiments demonstrated that the overexpression of FAT10 fostered the proliferation, migration, and invasion of HCC cells. Furthermore, the overexpression of FAT10 in HCC cells led to an increase in PD-L1 expression, resulting in the inhibition of T cell proliferation and the enhancement of HCC cell resistance to T cell-mediated cytotoxicity. Moreover, in vivo experiments utilizing the C57BL/6 mouse model revealed that overexpression of FAT10 effectively suppressed the infiltration of CD8 + GZMB + and CD8 + Ki67 + T cells, as well as reduced serum levels of TNF-α and IFN-γ. Mechanistically, we further identified that FAT10 upregulates PD-L1 expression via activating the PI3K/AKT/mTOR pathway, but not in a ubiquitin-like modification. In conclusion, our findings indicate that FAT10 promotes immune evasion of HCC via upregulating PD-L1 expression, suggesting its potential as a novel target to enhance the efficiency of immunotherapy in HCC.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 9-10","pages":"1529 - 1545"},"PeriodicalIF":6.1,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141185863","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":"Mechanisms of cuproptosis and its relevance to distinct diseases","authors":"Qiao-mei Lou,&nbsp;Fei-fan Lai,&nbsp;Jing-wei Li,&nbsp;Kun-jun Mao,&nbsp;Hai-tong Wan,&nbsp;Yu He","doi":"10.1007/s10495-024-01983-0","DOIUrl":"10.1007/s10495-024-01983-0","url":null,"abstract":"<div><p>Copper is a trace element required by the organism, but once the level of copper exceeds the threshold, it becomes toxic and even causes death. The underlying mechanisms of copper-induced death are inconclusive, with different studies showing different opinions on the mechanism of copper-induced death. Multiple investigations have shown that copper induces oxidative stress, endoplasmic reticulum stress, nucleolar stress, and proteasome inhibition, all of which can result in cell death. The latest research elucidates a copper-dependent death and denominates it as cuproptosis. Cuproptosis takes place through the combination of copper and lipoylated proteins of the tricarboxylic acid cycle, triggering agglomeration of lipoylated proteins and loss of iron-sulfur cluster proteins, leading to proteotoxic stress and ultimately death. Given the toxicity and necessity of copper, abnormal levels of copper lead to diseases such as neurological diseases and cancer. The development of cancer has a high demand for copper, neurological diseases involve the change of copper contents and the binding of copper to proteins. There is a close relationship between these two kinds of diseases and copper. Here, we summarize the mechanisms of copper-related death, and the association between copper and diseases, to better figure out the influence of copper in cell death and diseases, thus advancing the clinical remedy of these diseases.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 7-8","pages":"981 - 1006"},"PeriodicalIF":6.1,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141185896","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":"Exploring caspase functions in mouse models","authors":"Eva Svandova,&nbsp;Barbora Vesela,&nbsp;Eva Janeckova,&nbsp;Yang Chai,&nbsp;Eva Matalova","doi":"10.1007/s10495-024-01976-z","DOIUrl":"10.1007/s10495-024-01976-z","url":null,"abstract":"<div><p>Caspases are enzymes with protease activity. Despite being known for more than three decades, caspase investigation still yields surprising and fascinating information. Initially associated with cell death and inflammation, their functions have gradually been revealed to extend beyond, targeting pathways such as cell proliferation, migration, and differentiation. These processes are also associated with disease mechanisms, positioning caspases as potential targets for numerous pathologies including inflammatory, neurological, metabolic, or oncological conditions. While in vitro studies play a crucial role in elucidating molecular pathways, they lack the context of the body’s complexity. Therefore, laboratory animals are an indispensable part of successfully understanding and applying caspase networks. This paper aims to summarize and discuss recent knowledge, understanding, and challenges in caspase knock-out mice.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 7-8","pages":"938 - 966"},"PeriodicalIF":6.1,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11263464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141185778","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":"Integrated analysis reveals a novel 5-fluorouracil resistance-based prognostic signature with promising implications for predicting the efficacy of chemotherapy and immunotherapy in patients with colorectal cancer","authors":"Yufang Hou,&nbsp;Fang Zhang,&nbsp;Jinbao Zong,&nbsp;Tiegang Li,&nbsp;Wenqiang Gan,&nbsp;Silin Lv,&nbsp;Zheng Yan,&nbsp;Zifan Zeng,&nbsp;Liu Yang,&nbsp;Mingxuan Zhou,&nbsp;Wenyi Zhao,&nbsp;Min Yang","doi":"10.1007/s10495-024-01981-2","DOIUrl":"10.1007/s10495-024-01981-2","url":null,"abstract":"<div><p>Background: 5-Fluorouracil (5-FU) has been used as a standard first-line treatment for colorectal cancer (CRC) patients. Although 5-FU-based chemotherapy and immune checkpoint blockade (ICB) have achieved success in treating CRC, drug resistance and low response rates remain substantial limitations. Thus, it is necessary to construct a 5-FU resistance-related signature (5-FRSig) to predict patient prognosis and identify ideal patients for chemotherapy and immunotherapy. Methods: Using bulk and single-cell RNA sequencing data, we established and validated a novel 5-FRSig model using stepwise regression and multiple CRC cohorts and evaluated its associations with the prognosis, clinical features, immune status, immunotherapy, neoadjuvant therapy, and drug sensitivity of CRC patients through various bioinformatics algorithms. Unsupervised consensus clustering was performed to categorize the 5-FU resistance-related molecular subtypes of CRC. The expression levels of 5-FRSig, immune checkpoints, and immunoregulators were determined using quantitative real-time polymerase chain reaction (RT‒qPCR). Potential small-molecule agents were identified via Connectivity Map (CMap) and molecular docking. Results: The 5-FRSig and cluster were confirmed as independent prognostic factors in CRC, as patients in the low-risk group and Cluster 1 had a better prognosis. Notably, 5-FRSig was significantly associated with 5-FU sensitivity, chemotherapy response, immune cell infiltration, immunoreactivity phenotype, immunotherapy efficiency, and drug selection. We predicted 10 potential compounds that bind to the core targets of 5-FRSig with the highest affinity. Conclusion: We developed a valid 5-FRSig to predict the prognosis, chemotherapeutic response, and immune status of CRC patients, thus optimizing the therapeutic benefits of chemotherapy combined with immunotherapy, which can facilitate the development of personalized treatments and novel molecular targeted therapies for patients with CRC.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 7-8","pages":"1126 - 1144"},"PeriodicalIF":6.1,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141185874","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":"TBC1D10B promotes tumor progression in colon cancer via PAK4‑mediated promotion of the PI3K/AKT/mTOR pathway","authors":"Xiao-Jv Chi,&nbsp;Yi-Bei Song,&nbsp;Haoran Zhang,&nbsp;Li-Qiang Wei,&nbsp;Yong Gao,&nbsp;Xue-Jing Miao,&nbsp;Shu-Ting Yang,&nbsp;Chun-Yu Lin,&nbsp;Dong Lan,&nbsp;Xiquan Zhang","doi":"10.1007/s10495-024-01972-3","DOIUrl":"10.1007/s10495-024-01972-3","url":null,"abstract":"<div><p>This study aimed to explore the expression, function, and mechanisms of TBC1D10B in colon cancer, as well as its potential applications in the diagnosis and treatment of the disease.The expression levels of TBC1D10B in colon cancer were assessed by analyzing the TCGA and CCLE databases. Immunohistochemistry analysis was conducted using tumor and adjacent non-tumor tissues from 68 colon cancer patients. Lentiviral infection techniques were employed to silence and overexpress TBC1D10B in colon cancer cells. The effects on cell proliferation, migration, and invasion were evaluated using CCK-8, EDU, wound healing, and Transwell invasion assays. Additionally, GSEA enrichment analysis was used to explore the association of TBC1D10B with biological pathways related to colon cancer. TBC1D10B was significantly upregulated in colon cancer and closely associated with patient prognosis. Silencing of TBC1D10B notably inhibited proliferation, migration, and invasion of colon cancer cells and promoted apoptosis. Conversely, overexpression of TBC1D10B enhanced these cellular functions. GSEA analysis revealed that TBC1D10B is enriched in the AKT/PI3K/mTOR signaling pathway and highly correlated with PAK4. The high expression of TBC1D10B in colon cancer is associated with poor prognosis. It influences cancer progression by regulating the proliferation, migration, and invasion capabilities of colon cancer cells, potentially acting through the AKT/PI3K/mTOR signaling pathway. These findings provide new targets and therapeutic strategies for the treatment of colon cancer.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 7-8","pages":"1185 - 1197"},"PeriodicalIF":6.1,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141185900","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}