Apoptosis最新文献_第4页

TNF-α and RPLP0 drive the apoptosis of endothelial cells and increase susceptibility to high-altitude pulmonary edema TNF-α 和 RPLP0 驱动内皮细胞凋亡，增加高海拔肺水肿的易感性。

IF 6.1 2区生物学

Apoptosis Pub Date : 2024-08-07 DOI: 10.1007/s10495-024-02005-9

Yi-Ling Ge, Pei-Jie Li, Ying-Rui Bu, Bin Zhang, Jin Xu, Si-Yuan He, Qing-Lin Cao, Yun-Gang Bai, Jin Ma, Lin Zhang, Jie Zhou, Man-Jiang Xie

{"title":"TNF-α and RPLP0 drive the apoptosis of endothelial cells and increase susceptibility to high-altitude pulmonary edema","authors":"Yi-Ling Ge, Pei-Jie Li, Ying-Rui Bu, Bin Zhang, Jin Xu, Si-Yuan He, Qing-Lin Cao, Yun-Gang Bai, Jin Ma, Lin Zhang, Jie Zhou, Man-Jiang Xie","doi":"10.1007/s10495-024-02005-9","DOIUrl":"10.1007/s10495-024-02005-9","url":null,"abstract":"<div><p>High-altitude pulmonary edema (HAPE) is a fatal threat for sojourners who ascend rapidly without sufficient acclimatization. Acclimatized sojourners and adapted natives are both insensitive to HAPE but have different physiological traits and molecular bases. In this study, based on GSE52209, the gene expression profiles of HAPE patients were compared with those of acclimatized sojourners and adapted natives, with the common and divergent differentially expressed genes (DEGs) and their hub genes identified, respectively. Bioinformatic methodologies for functional enrichment analysis, immune infiltration, diagnostic model construction, competing endogenous RNA (ceRNA) analysis and drug prediction were performed to detect potential biological functions and molecular mechanisms. Next, an array of in vivo experiments in a HAPE rat model and in vitro experiments in HUVECs were conducted to verify the results of the bioinformatic analysis. The enriched pathways of DEGs and immune landscapes for HAPE were significantly different between sojourners and natives, and the common DEGs were enriched mainly in the pathways of development and immunity. Nomograms revealed that the upregulation of TNF-α and downregulation of RPLP0 exhibited high diagnostic efficiency for HAPE in both sojourners and natives, which was further validated in the HAPE rat model. The addition of TNF-α and RPLP0 knockdown activated apoptosis signaling in endothelial cells (ECs) and enhanced endothelial permeability. In conclusion, TNF-α and RPLP0 are shared biomarkers and molecular bases for HAPE susceptibility during the acclimatization/adaptation/maladaptation processes in sojourners and natives, inspiring new ideas for predicting and treating HAPE.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 9-10","pages":"1600 - 1618"},"PeriodicalIF":6.1,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896610","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}

引用次数: 0

Correction: Targeting PNPO to suppress tumor growth via inhibiting autophagic flux and to reverse paclitaxel resistance in ovarian cancer 更正：以 PNPO 为靶点，通过抑制自噬通量抑制肿瘤生长，并逆转卵巢癌对紫杉醇的耐药性。

IF 6.1 2区生物学

Apoptosis Pub Date : 2024-08-04 DOI: 10.1007/s10495-024-01998-7

Xin Li, Wencai Guan, Huiqiang Liu, Jia Yuan, Fanchen Wang, Bin Guan, Junyu Chen, Qi Lu, Lingyun Zhang, Guoxiong Xu

引用次数: 0

Comprehensive pancancer analysis reveals that LPCAT1 is a novel predictive biomarker for prognosis and immunotherapy response 胰腺癌综合分析表明，LPCAT1 是预测预后和免疫疗法反应的新型生物标志物。

IF 6.1 2区生物学

Apoptosis Pub Date : 2024-08-04 DOI: 10.1007/s10495-024-02010-y

Hongyu Gao, Jinfeng Zhu, Tong Wu, Qian Long, Xinyu Guan, Qitong Chen, Wenjun Yi

{"title":"Comprehensive pancancer analysis reveals that LPCAT1 is a novel predictive biomarker for prognosis and immunotherapy response","authors":"Hongyu Gao, Jinfeng Zhu, Tong Wu, Qian Long, Xinyu Guan, Qitong Chen, Wenjun Yi","doi":"10.1007/s10495-024-02010-y","DOIUrl":"10.1007/s10495-024-02010-y","url":null,"abstract":"<div><p>Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is a crucial enzyme involved in phospholipid metabolism and is essential for maintaining the structure and functionality of biofilms. However, a comprehensive examination of the role of LPCAT1 across various cancer types is lacking. Multiple public databases have been utilized to examine LPCAT1 expression, genetic alterations, methylation, prognosis, biological function, and its relationship with antitumor immunity in different cancer types. The function of LPCAT1 in glioma, breast cancer and liver cancer cells was further verified using in vitro experiments. Our research indicated that LPCAT1 is upregulated in various cancers and is accompanied by a wide range of amplification mutations. Higher LPCAT1 expression was associated with poorer prognosis across multiple cancers. Further in vitro experiments demonstrated that interfering with LPCAT1 expression increased apoptosis in glioma, breast cancer and liver cancer cells and concurrently suppressed their proliferation and migration. Functional enrichment analysis revealed that LPCAT1-associated genes were primarily enriched in immune and cancer progression pathways, such as the JAK/STAT, MYC, and EMT, etc. Moreover, LPCAT1 expression was closely associated with immune cell infiltration and immune checkpoint-related gene expression. Interestingly, LPCAT1 expression levels were generally higher in patients in the immunotherapy response group. The combination of LPCAT1 and PDL1 serves as an effective predictor of immunotherapy response. In conclusion, LPCAT1 is involved in immune regulation and tumor progression and holds promise as a biomarker for predicting patient outcomes and immunotherapy efficacy.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 11-12","pages":"2128 - 2146"},"PeriodicalIF":6.1,"publicationDate":"2024-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888303","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}

引用次数: 0

SEH1L siliencing induces ferroptosis and suppresses hepatocellular carcinoma progression via ATF3/HMOX1/GPX4 axis SEH1L siliencing通过ATF3/HMOX1/GPX4轴诱导铁变态反应并抑制肝细胞癌的进展。

IF 6.1 2区生物学

Apoptosis Pub Date : 2024-08-02 DOI: 10.1007/s10495-024-02009-5

Ziyang Feng, Ke Cao, Haojia Sun, Xuewen Liu

{"title":"SEH1L siliencing induces ferroptosis and suppresses hepatocellular carcinoma progression via ATF3/HMOX1/GPX4 axis","authors":"Ziyang Feng, Ke Cao, Haojia Sun, Xuewen Liu","doi":"10.1007/s10495-024-02009-5","DOIUrl":"10.1007/s10495-024-02009-5","url":null,"abstract":"<div><p>SEH1 like nucleoporin (SEH1L) is an important component of nuclear pore complex (NPC), which is crucial in the regulation of cell division. However, the interrelation between SEH1L expression and tumor progression is less studied. In this research, we performed a systematic bioinformatic analysis about SEH1L using TCGA, Timer 2.0, Cbioportal, UCLAN and CellMiner™ databases in pan-cancer. Besides, we further validated the bioinformatic results through in vitro and in vivo experiments in HCC, including transcriptome sequencing, real-time quantitative PCR (RT-qPCR), western blotting (WB), immunohistochemistry (IHC), cell proliferation assays, clone formation, EdU, transwell, flow cytometry and subcutaneous tumor model. Our results suggested that SEH1L was significantly up-regulated and related to poor prognosis in most cancers, and may serve as a potential biomarker. SEH1L could promote HCC progression in vitro and in vivo. Besides, the next generation sequencing suggested that 684 genes was significantly up-regulated and 678 genes was down-regulated after the knock down of SEH1L. SEH1L siliencing could activate ATF3/HMOX1/GPX4 axis, decrease mitochondrial membrane potential and GSH, but increase ROS and MDA, and these effects could be reversed by the knock down of ATF3. This study indicated that SEH1L siliencing could induce ferroptosis and suppresses hepatocellular carcinoma (HCC) progression via ATF3/HMOX1/GPX4 axis.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 9-10","pages":"1723 - 1737"},"PeriodicalIF":6.1,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878249","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}

引用次数: 0

Strong activation of p53 by actinomycin D and nutlin-3a overcomes the resistance of cancer cells to the pro-apoptotic activity of the FAS ligand 放线菌素 D 和 nutlin-3a 强力激活 p53，克服了癌细胞对 FAS 配体促凋亡活性的抵抗力

IF 6.1 2区生物学

Apoptosis Pub Date : 2024-07-28 DOI: 10.1007/s10495-024-02000-0

Barbara Łasut-Szyszka, Agnieszka Gdowicz-Kłosok, Małgorzata Krześniak, Magdalena Głowala-Kosińska, Agnieszka Będzińska, Marek Rusin

{"title":"Strong activation of p53 by actinomycin D and nutlin-3a overcomes the resistance of cancer cells to the pro-apoptotic activity of the FAS ligand","authors":"Barbara Łasut-Szyszka, Agnieszka Gdowicz-Kłosok, Małgorzata Krześniak, Magdalena Głowala-Kosińska, Agnieszka Będzińska, Marek Rusin","doi":"10.1007/s10495-024-02000-0","DOIUrl":"10.1007/s10495-024-02000-0","url":null,"abstract":"<div><p>The FAS ligand (FASLG) is expressed on lymphocytes, which employ it to activate death receptors on target cells. Cancer cells are generally resistant to apoptosis triggered by FASLG. In this work, we found a way to circumvent this resistance by treatment with actinomycin D (ActD) and nutlin-3a (Nut3a). We selected this drug combination based on our transcriptomic data showing strong activation of proapoptotic genes, including those for receptor-mediated apoptosis, in cells exposed to actinomycin D and nutlin-3a. To test our hypothesis, we pre-exposed cancer cell lines to this drug combination for 45 h and then treated them with recombinant FASLG. This almost instantaneously killed most cells. Actinomycin D and nutlin-3a strongly cooperated in the sensitization because the effect of the drugs acting solo was not as spectacular as the drug combination, which together with FASLG killed more than 99% of cells. Based on the caspase activation pattern (caspase-8, caspase-9, caspase-10), we conclude that both extrinsic and intrinsic pro-apoptotic pathways were engaged. In engineered p53-deficient cells, this pro-apoptotic effect was completely abrogated. Therefore, the combination of ActD + Nut3a activates p53 in an extraordinary way, which overcomes the resistance of cancer cells to apoptosis triggered by FASLG. Interestingly, other combinations of drugs, e.g., etoposide + nutlin-3a, actinomycin D + RG7112, and actinomycin D + idasanutlin had a similar effect. Moreover, normal human fibroblasts are less sensitive to death induced by ActD + Nut3a + FASLG. Our findings create the opportunity to revive the abandoned attempts of cancer immunotherapy employing the recombinant FAS ligand.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 9-10","pages":"1515 - 1528"},"PeriodicalIF":6.1,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-024-02000-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141784093","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}

引用次数: 0

Glutamine deprivation in glioblastoma stem cells triggers autophagic SIRT3 degradation to epigenetically restrict CD133 expression and stemness 胶质母细胞瘤干细胞中的谷氨酰胺匮乏会引发自噬性SIRT3降解，从而从表观遗传学上限制CD133的表达和干性

IF 6.1 2区生物学

Apoptosis Pub Date : 2024-07-28 DOI: 10.1007/s10495-024-02003-x

Zhengcao Xing, Xianguo Jiang, Yalan Chen, Tiange Wang, Xiaohe Li, Xiangyun Wei, Qiuju Fan, Jie Yang, Hongmei Wu, Jinke Cheng, Rong Cai

{"title":"Glutamine deprivation in glioblastoma stem cells triggers autophagic SIRT3 degradation to epigenetically restrict CD133 expression and stemness","authors":"Zhengcao Xing, Xianguo Jiang, Yalan Chen, Tiange Wang, Xiaohe Li, Xiangyun Wei, Qiuju Fan, Jie Yang, Hongmei Wu, Jinke Cheng, Rong Cai","doi":"10.1007/s10495-024-02003-x","DOIUrl":"10.1007/s10495-024-02003-x","url":null,"abstract":"<div><p>Glioblastoma multiforme (GBM) is a highly malignant brain tumor, and glioblastoma stem cells (GSCs) are the primary cause of GBM heterogeneity, invasiveness, and resistance to therapy. Sirtuin 3 (SIRT3) is mainly localized in the mitochondrial matrix and plays an important role in maintaining GSC stemness through cooperative interaction with the chaperone protein tumor necrosis factor receptor-associated protein 1 (TRAP1) to modulate mitochondrial respiration and oxidative stress. The present study aimed to further elucidate the specific mechanisms by which SIRT3 influences GSC stemness, including whether SIRT3 serves as an autophagy substrate and the mechanism of SIRT3 degradation. We first found that SIRT3 is enriched in CD133<sup>+</sup> GSCs. Further experiments revealed that in addition to promoting mitochondrial respiration and reducing oxidative stress, SIRT3 maintains GSC stemness by epigenetically regulating CD133 expression <i>via</i> succinate. More importantly, we found that SIRT3 is degraded through the autophagy–lysosome pathway during GSC differentiation into GBM bulk tumor cells. GSCs are highly dependent on glutamine for survival, and in these cells, we found that glutamine deprivation triggers autophagic SIRT3 degradation to restrict CD133 expression, thereby disrupting the stemness of GSCs. Together our results reveal a novel mechanism by which SIRT3 regulates GSC stemness. We propose that glutamine restriction to trigger autophagic SIRT3 degradation offers a strategy to eliminate GSCs, which combined with other treatment methods may overcome GBM resistance to therapy as well as relapse.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 9-10","pages":"1619 - 1631"},"PeriodicalIF":6.1,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141784092","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}

引用次数: 0

Sphingolipid metabolism and regulated cell death in malignant melanoma 恶性黑色素瘤中的鞘脂代谢和调节性细胞死亡

IF 6.1 2区生物学

Apoptosis Pub Date : 2024-07-28 DOI: 10.1007/s10495-024-02002-y

Kexin Yan, Wei Zhang, Hao Song, Xiulian Xu

引用次数: 0

CD8 + CD103 + iTregs protect against ischemia-reperfusion-induced acute kidney Injury by inhibiting pyroptosis CD8 + CD103 + iTregs 通过抑制热蛋白沉积防止缺血再灌注诱发的急性肾损伤

IF 6.1 2区生物学

Apoptosis Pub Date : 2024-07-28 DOI: 10.1007/s10495-024-02001-z

Qiuju Chen, Xiao Zhang, Hui Yang, Guangxuan Luo, Xin Zhou, Zhenjian Xu, Anping Xu

{"title":"CD8 + CD103 + iTregs protect against ischemia-reperfusion-induced acute kidney Injury by inhibiting pyroptosis","authors":"Qiuju Chen, Xiao Zhang, Hui Yang, Guangxuan Luo, Xin Zhou, Zhenjian Xu, Anping Xu","doi":"10.1007/s10495-024-02001-z","DOIUrl":"10.1007/s10495-024-02001-z","url":null,"abstract":"<div><p>The occurrence of acute kidney injury (AKI) is elevated, one of the main causes is ischemia-reperfusion (I/R). However, no specific therapy is currently available to treat I/R-induced AKI (I/R-AKI). Treg cells have been demonstrated to perform an anti-inflammatory role in a range of autoimmune and inflammatory illnesses. However, there is limited available information about the possible functions of CD8 + CD103 + iTregs in I/R-AKI. We utilized renal tubular epithelial cells (RTECs) subjected to hypoxia-reoxygenation (H/R) and I/R-AKI mouse model to investigate whether CD8 + CD103 + iTregs could attenuate AKI and the underlying mechanism. In vitro, co-cultured with CD8 + CD103 + iTregs alleviated H/R-induced cell injury. After treatment of CD8 + CD103 + iTregs rather than control cells, a significant improvement of I/R-AKI was observed in vivo, including decreased serum creatinine (sCr) and blood urea nitrogen (BUN) levels, reduced renal pathological injury, lowered tubular apoptosis and inhibition of the transition from AKI to chronic kidney disease (CKD). Mechanically, CD8 + CD103 + iTregs alleviated H/R-induced cell injury and I/R-AKI partly by suppressing RTECs pyroptosis via inhibiting the NLRP3/Caspase-1 axis. Our study provides a novel perspective on the possibility of CD8 + CD103 + iTregs for the treatment of I/R-AKI.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 9-10","pages":"1709 - 1722"},"PeriodicalIF":6.1,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141784090","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}

引用次数: 0

PTGR1-mediated immune evasion mechanisms in late-stage triple-negative breast cancer: mechanisms of M2 macrophage infiltration and CD8+ T cell suppression 晚期三阴性乳腺癌中 PTGR1 介导的免疫逃避机制：M2 巨噬细胞浸润和 CD8+ T 细胞抑制机制

IF 6.1 2区生物学

Apoptosis Pub Date : 2024-07-28 DOI: 10.1007/s10495-024-01991-0

Fang Huang, Fuhe Wang, Qilu Hu, Ying Li, Da Jiang

{"title":"PTGR1-mediated immune evasion mechanisms in late-stage triple-negative breast cancer: mechanisms of M2 macrophage infiltration and CD8+ T cell suppression","authors":"Fang Huang, Fuhe Wang, Qilu Hu, Ying Li, Da Jiang","doi":"10.1007/s10495-024-01991-0","DOIUrl":"10.1007/s10495-024-01991-0","url":null,"abstract":"<div><p>Triple-negative breast cancer (TNBC) is a heterogeneous disease characterized by metabolic dysregulation. Tumor cell immune escape plays an indispensable role in the development of TNBC tumors. Furthermore, in the abstract, we explicitly mention the techniques used and enhance the clarity and impact of our findings. “Based on bioinformatics analysis results, we utilized CRISPR/Cas9 technology to knockout the target gene and established a mouse model of breast cancer. Through experiments such as CCK8, scratch assay, and Transwell assay, we further investigated the impact of target gene knockout on the malignant behavior of tumor cells. Subsequently, we conducted immunohistochemistry and Western Blot experiments to study the expression of macrophage polarization and infiltration-related markers and evaluate the effect of the target gene on macrophage polarization. Next, through co-culture experiments, we simulated the tumor microenvironment and used immunohistochemistry staining to observe and analyze the distribution and activation status of M2 macrophages and CD8<sup>+</sup> T cells in the co-culture system. We validated in vivo experiments the molecular mechanism by which the target gene regulates immune cell impact on TNBC progression.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 11-12","pages":"2002 - 2024"},"PeriodicalIF":6.1,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-024-01991-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141784091","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}

引用次数: 0

The resistance to anoikis, mediated by Spp1, and the evasion of immune surveillance facilitate the invasion and metastasis of hepatocellular carcinoma 由 Spp1 介导的对 anoikis 的抗性和对免疫监视的规避促进了肝细胞癌的入侵和转移

IF 6.1 2区生物学

Apoptosis Pub Date : 2024-07-27 DOI: 10.1007/s10495-024-01994-x

Zhengwei Zhang, Xiaoning Chen, Yapeng Li, Feng Zhang, Zhen Quan, Zhuo Wang, Yang Yang, Wei Si, Yuting Xiong, Jiaming Ju, Yu Bian, Shibo Sun

{"title":"The resistance to anoikis, mediated by Spp1, and the evasion of immune surveillance facilitate the invasion and metastasis of hepatocellular carcinoma","authors":"Zhengwei Zhang, Xiaoning Chen, Yapeng Li, Feng Zhang, Zhen Quan, Zhuo Wang, Yang Yang, Wei Si, Yuting Xiong, Jiaming Ju, Yu Bian, Shibo Sun","doi":"10.1007/s10495-024-01994-x","DOIUrl":"10.1007/s10495-024-01994-x","url":null,"abstract":"<div><p>Anoikis-Related Genes (ARGs) lead to the organism manifesting resistance to anoikis and are associated with unfavorable prognostic outcomes across various malignancies.Therefore, it is crucial to identify the pivotal target genes related to anoikis in HCC .We found that ARGs were significantly correlated with prognosis and immune responses in HCC. The core gene, SPP1, notably promoted anoikis resistance and metastasis in HCC through both in vivo and in vitro studies. The PI3K-Akt-mTOR pathway played a critical role in anoikis suppression within HCC contexts. Our research unveiled SPP1’s role in enhancing PKCα phosphorylation, which in turn activated the PI3K-Akt-mTOR cascade. Additionally, SPP1 was identified as a key regulator of MDSCs and Tregs migration, directly affecting their immunosuppressive capabilities.These findings indicate that in HCC, SPP1 promoted anoikis resistance and facilitated immune evasion by modulating MDSCs and Tregs.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 9-10","pages":"1564 - 1583"},"PeriodicalIF":6.1,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-024-01994-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141783994","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}

引用次数: 0