Oncogene最新文献_第7页

Editorial Expression of Concern: Sensitization for death receptor- or drug-induced apoptosis by re-expression of caspase-8 through demethylation or gene transfer 社论表达关切：通过去甲基化或基因转移重新表达 caspase-8，对死亡受体或药物诱导的细胞凋亡敏感。

IF 6.9 1区医学

Oncogene Pub Date : 2024-09-06 DOI: 10.1038/s41388-024-03158-2

Simone Fulda, Martin U. Kuüfer, Eric Meyer, Frans van Valen, Barbara Dockhorn-Dworniczak, Klaus-Michael Debatin

引用次数: 0

Editorial Expression of Concern: RAFTK/PYK2-dependent and -independent apoptosis in multiple myeloma cells 社论表达关注：RAFTK/PYK2依赖性和非依赖性多发性骨髓瘤细胞凋亡。

IF 6.9 1区医学

Oncogene Pub Date : 2024-09-05 DOI: 10.1038/s41388-024-03152-8

Dharminder Chauhan, Teru Hideshima, Pramod Pandey, Steve Treon, Gerrard Teoh, Noopur Raje, Steven Rosen, Nancy Krett, Hervé Husson, Shalom Avraham, Surender Kharbanda, Kenneth C. Anderson

引用次数: 0

PPM1D activity promotes cellular transformation by preventing senescence and cell death PPM1D 的活性通过防止衰老和细胞死亡来促进细胞转化。

IF 6.9 1区医学

Oncogene Pub Date : 2024-09-05 DOI: 10.1038/s41388-024-03149-3

Miroslav Stoyanov, Andra S. Martinikova, Katerina Matejkova, Klara Horackova, Petra Zemankova, Kamila Burdova, Zuzana Zemanova, Petra Kleiblova, Zdenek Kleibl, Libor Macurek

{"title":"PPM1D activity promotes cellular transformation by preventing senescence and cell death","authors":"Miroslav Stoyanov, Andra S. Martinikova, Katerina Matejkova, Klara Horackova, Petra Zemankova, Kamila Burdova, Zuzana Zemanova, Petra Kleiblova, Zdenek Kleibl, Libor Macurek","doi":"10.1038/s41388-024-03149-3","DOIUrl":"10.1038/s41388-024-03149-3","url":null,"abstract":"Cell cycle checkpoints, oncogene-induced senescence and programmed cell death represent intrinsic barriers to tumorigenesis. Protein phosphatase magnesium-dependent 1 (PPM1D) is a negative regulator of the tumour suppressor p53 and has been implicated in termination of the DNA damage response. Here, we addressed the consequences of increased PPM1D activity resulting from the gain-of-function truncating mutations in exon 6 of the PPM1D. We show that while control cells permanently exit the cell cycle and reside in senescence in the presence of DNA damage caused by ionising radiation or replication stress induced by the active RAS oncogene, RPE1-hTERT and BJ-hTERT cells carrying the truncated PPM1D continue proliferation in the presence of DNA damage, form micronuclei and accumulate genomic rearrangements revealed by karyotyping. Further, we show that increased PPM1D activity promotes cell growth in the soft agar and formation of tumours in xenograft models. Finally, expression profiling of the transformed clones revealed dysregulation of several oncogenic and tumour suppressor pathways. Our data support the oncogenic potential of PPM1D in the context of exposure to ionising radiation and oncogene-induced replication stress.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-024-03149-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sorafenib-mediated cleavage of p62 initiates cellular senescence as a mechanism to evade its anti-hepatocellular carcinoma efficacy 索拉非尼介导的p62裂解引发细胞衰老是一种逃避其抗肝细胞癌疗效的机制。

IF 6.9 1区医学

Oncogene Pub Date : 2024-09-04 DOI: 10.1038/s41388-024-03142-w

Jiaying Du, Dongsheng Bai, Chunyang Gu, Jiawei Zhao, Chen Zhou, Yuxiang Wang, Yue Zhao, Na Lu

{"title":"Sorafenib-mediated cleavage of p62 initiates cellular senescence as a mechanism to evade its anti-hepatocellular carcinoma efficacy","authors":"Jiaying Du, Dongsheng Bai, Chunyang Gu, Jiawei Zhao, Chen Zhou, Yuxiang Wang, Yue Zhao, Na Lu","doi":"10.1038/s41388-024-03142-w","DOIUrl":"10.1038/s41388-024-03142-w","url":null,"abstract":"Hepatocellular carcinoma (HCC) stands as one of the most aggressively advancing and lethal malignancies. Sorafenib is presently endorsed as a primary therapy for advanced liver cancer, but its resistance presents a formidable challenge. Previous studies have implicated a connection between post-sorafenib discontinuation rebound and the development of drug resistance, yet the underlying mechanism remains elusive. In this study, we discerned that Sorafenib induced a senescent phenotype in HCC cells and caused a cleavage of ubiquitin-binding protein p62. Mechanistic studies establish that truncated p62 drives cellular senescence by promoting proteasome-dependent degradation of 4EBP1. Furthermore, truncated p62 induced specific ubiquitination of 4EBP1. Crucially, virtual drug screening uncovered that dacinostat inhibited cellular senescence by blocking sorafenib-induced p62 cleavage. In summary, our findings imply that truncated p62 from sorafenib cleavage promotes senescence via 4EBP1 degradation. The prevention of p62 cleavage could emerge as a crucial strategy for impeding the sorafenib-induced cellular senescence.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-024-03142-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synergistic effects of combined BET and FAK inhibition against Vestibular Schwannomas in NF2-related Schwannomatosis 联合抑制 BET 和 FAK 对 NF2 相关性前庭神经丛神经瘤的协同作用

IF 6.9 1区医学

Oncogene Pub Date : 2024-08-29 DOI: 10.1038/s41388-024-03144-8

Maria A. González-Rodriguez, Scott Troutman, Simon Bayle, Daniel K. Lester, Matthew Grove, Derek Duckett, Michael S. Kareta, Joseph L. Kissil

{"title":"Synergistic effects of combined BET and FAK inhibition against Vestibular Schwannomas in NF2-related Schwannomatosis","authors":"Maria A. González-Rodriguez, Scott Troutman, Simon Bayle, Daniel K. Lester, Matthew Grove, Derek Duckett, Michael S. Kareta, Joseph L. Kissil","doi":"10.1038/s41388-024-03144-8","DOIUrl":"10.1038/s41388-024-03144-8","url":null,"abstract":"Neurofibromatosis type 2 (NF2) is a rare disorder that causes vestibular schwannomas (VS), meningiomas and ependymomas. To date, there is no FDA approved drug-based treatment for NF2. We have previously identified that BET inhibition can selectively reduce growth of the NF2-null schwannoma and Schwann cells in vitro and tumorigenesis in vivo and, separately, reported that inhibition of Focal Adhesion Kinase 1 (FAK1) via crizotinib has antiproliferative effects in NF2-null Schwann cells. The current study was aimed at determining whether combined BET and FAK inhibition can synergize and to identify the mechanisms of action. A panel of normal and NF2-null Schwann and schwannoma cell lines were used to characterize the effects of combined BET and FAK inhibition in vitro and in vivo using pharmacological and genetic approaches. The mechanism of action was explored by chromatin immunoprecipitation, ChIP-PCR, western blotting, and functional approaches. We find that combined BET and FAK inhibition are synergistic and inhibit the proliferation of NF2-null schwannoma and Schwann cell lines in vitro and in vivo, by arresting cells in the G1/S and G2/M phases of the cell cycle. Further, we identify the mechanism of action through the downregulation of FAK1 transcription by BET inhibition, which potentiates inhibition of FAK by 100-fold. Our findings suggest that combined targeting of BET and FAK1 may offer a potential therapeutic option for the treatment of NF2-related schwannomas.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-024-03144-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bioinformatics advances in eccDNA identification and analysis eccDNA鉴定和分析中的生物信息学进展。

IF 6.9 1区医学

Oncogene Pub Date : 2024-08-29 DOI: 10.1038/s41388-024-03138-6

Fuyu Li, Wenlong Ming, Wenxiang Lu, Ying Wang, Xianjun Dong, Yunfei Bai

引用次数: 0

Editorial Expression of Concern: p38 MAPK inhibition enhances PS-341 (bortezomib)-induced cytotoxicity against multiple myeloma cells 社论关注：抑制 p38 MAPK 可增强 PS-341（硼替佐米）诱导的多发性骨髓瘤细胞毒性。

IF 6.9 1区医学

Oncogene Pub Date : 2024-08-29 DOI: 10.1038/s41388-024-03147-5

Teru Hideshima, Klaus Podar, Dharminder Chauhan, Kenji Ishitsuka, Constantine Mitsiades, Yu-Tzu Tai, Makoto Hamasaki, Noopur Raje, Hiromasa Hideshima, George Schreiner, Aaron N. Nguyen, Tony Navas, Nikhil C. Munshi, Paul G. Richardson, Linda S. Higgins, Kenneth C. Anderson

引用次数: 0

m6A modification of lipoyltransferase 1 inhibits bladder cancer progression by activating cuproptosis 脂肪酰基转移酶 1 的 m6A 修饰通过激活杯突酶抑制膀胱癌的进展。

IF 6.9 1区医学

Oncogene Pub Date : 2024-08-28 DOI: 10.1038/s41388-024-03139-5

Kaixuan Du, Yongbo Luo, Lei Zhang, Youmiao Zeng, Yiheng Dai, Mengda Ren, Wenbang Pan, Yuanhao Liu, Fengyan Tian, Lijie Zhou, Chaohui Gu

{"title":"m6A modification of lipoyltransferase 1 inhibits bladder cancer progression by activating cuproptosis","authors":"Kaixuan Du, Yongbo Luo, Lei Zhang, Youmiao Zeng, Yiheng Dai, Mengda Ren, Wenbang Pan, Yuanhao Liu, Fengyan Tian, Lijie Zhou, Chaohui Gu","doi":"10.1038/s41388-024-03139-5","DOIUrl":"10.1038/s41388-024-03139-5","url":null,"abstract":"Cuproptosis, a cell death process caused by copper ions, is mediated by protein lipidation related to lipoic acid metabolism. There is a close connection between cuproptosis and the progression and prognosis of various tumors. Here, we identified lipoyltransferase 1 (LIPT1), a key gene related to cuproptosis, was downregulated in bladder cancer (BLCA) and was associated with unfavorable patient prognosis. Restoring the LIPT1 expression in BLCA cells suppressed the proliferation and promoted cuproptosis. Moreover, the consequences of RNA sequencing and Bodipy staining showed that the metabolic pathway mediated by LIPT1 inhibited the accumulation of lipid droplets in cells, disrupted endoplasmic reticulum (ER) homeostasis, and promoted cell apoptosis. Additionally, overexpression of LIPT1 not only repressed the proliferation rate of BLCA cells in vitro but also in vivo. Mechanistically, YTH N6-Methyladenosine RNA Binding Protein F2 (YTHDF2) promoted the degradation of LIPT1 mRNA in a m6A-dependent manner. In summary, these conclusions reveal that LIPT1 promotes cuprotosis and ER stress to inhibit the progression of BLCA, indicating that LIPT1 will provide a powerful treatment direction and drug target for treating BLCA.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-024-03139-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

S-p-bromobenzyl-glutathione cyclopentyl diester (BBGC) as novel therapeutic strategy to enhance trabectedin anti-tumor effect in soft tissue sarcoma preclinical models S-对溴苄基谷胱甘肽环戊基二酯（BBGC）作为一种新型治疗策略，可增强曲贝替定在软组织肉瘤临床前模型中的抗肿瘤效果。

IF 6.9 1区医学

Oncogene Pub Date : 2024-08-28 DOI: 10.1038/s41388-024-03143-9

F. Pantano, S. Simonetti, M. Iuliani, M. J. Guillen, C. Cuevas, P. Aviles, S. Cavaliere, A. Napolitano, A. Cortellini, A. Mazzocca, L. Nibid, G. Sabarese, G. Perrone, M. Gambarotti, A. Righi, E. Palmerini, S. Stacchiotti, M. Barisella, A. Gronchi, S. Valeri, M. Sbaraglia, A. P. Dei Tos, G. Tonini, B. Vincenzi

{"title":"S-p-bromobenzyl-glutathione cyclopentyl diester (BBGC) as novel therapeutic strategy to enhance trabectedin anti-tumor effect in soft tissue sarcoma preclinical models","authors":"F. Pantano, S. Simonetti, M. Iuliani, M. J. Guillen, C. Cuevas, P. Aviles, S. Cavaliere, A. Napolitano, A. Cortellini, A. Mazzocca, L. Nibid, G. Sabarese, G. Perrone, M. Gambarotti, A. Righi, E. Palmerini, S. Stacchiotti, M. Barisella, A. Gronchi, S. Valeri, M. Sbaraglia, A. P. Dei Tos, G. Tonini, B. Vincenzi","doi":"10.1038/s41388-024-03143-9","DOIUrl":"10.1038/s41388-024-03143-9","url":null,"abstract":"Trabectedin, approved for the treatment of soft tissue sarcoma (STS), interferes with cell division and genetic transcription processes. Due to its strong anti-tumor activity in only certain histotypes, several studies on trabectedin combinations are currently ongoing to improve its efficacy. In this study, we aimed to investigate novel potential therapeutic strategies to enhance the anti-tumor effect of trabectedin using integrated in silico, in vitro, and in vivo approaches. For in silico analysis, we screened two public datasets, GSEA M5190 and TCGA SARC. Fibrosarcoma, leiomyosarcoma, dedifferentiated, and myxoid liposarcoma cell lines were used for in vitro studies. For in vivo experiments, fibrosarcoma orthotopic murine model was developed. In silico analysis identified Glo1 as the only druggable target upregulated after trabectedin treatment and correlated with poor prognosis. The specific Glo1 inhibitor, S-p-bromobenzylglutathione cyclopentyl diester (BBGC), increased trabectedin cytotoxicity in STS cells, and restored drug sensitivity in myxoid liposarcoma cells resistant to trabectedin. Moreover, the combined treatment with BBGC and trabectedin had a synergistic antitumor effect in vivo without any additional toxicity to mice. Based on these results, we believe that BBGC warrants further investigation to evaluate its potential clinical use in combination with trabectedin.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-024-03143-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RBM12 drives PD-L1-mediated immune evasion in hepatocellular carcinoma by increasing JAK1 mRNA translation RBM12通过增加JAK1 mRNA的翻译来驱动肝细胞癌中PD-L1介导的免疫逃避。

IF 6.9 1区医学

Oncogene Pub Date : 2024-08-26 DOI: 10.1038/s41388-024-03140-y

Hexu Han, Qian Shi, Yue Zhang, Mingdong Ding, Xianzhong He, Cuixia Liu, Dakun Zhao, Yifan Wang, Yanping Du, Yichao Zhu, Yin Yuan, Siliang Wang, Huimin Guo, Qiang Wang

{"title":"RBM12 drives PD-L1-mediated immune evasion in hepatocellular carcinoma by increasing JAK1 mRNA translation","authors":"Hexu Han, Qian Shi, Yue Zhang, Mingdong Ding, Xianzhong He, Cuixia Liu, Dakun Zhao, Yifan Wang, Yanping Du, Yichao Zhu, Yin Yuan, Siliang Wang, Huimin Guo, Qiang Wang","doi":"10.1038/s41388-024-03140-y","DOIUrl":"10.1038/s41388-024-03140-y","url":null,"abstract":"Immunosuppression characterizes the tumour microenvironment in HCC, and recent studies have implicated RNA-binding proteins (RBPs) in the development of HCC. Here, we conducted a screen and identified RBM12 as a key protein that increased the expression of PD-L1, thereby driving immune evasion in HCC. Furthermore, RBM12 was found to be significantly upregulated in HCC tissues and was associated with a poor prognosis for HCC patients. Through various molecular assays and high-throughput screening, we determined that RBM12 could directly bind to the JAK1 mRNA via its 4th-RRM (RNA recognition motif) domain and recruit EIF4A2 through its 2nd-RRM domain, enhancing the distribution of ribosomes on JAK1 mRNA, which promotes the translation of JAK1 and the subsequent upregulation of its expression. As a result, the activated JAK1/STAT1 pathway transcriptionally upregulates PD-L1 expression, facilitating immune evasion in HCC. In summary, our findings provide insights into the significant contribution of RBM12 to immune evasion in HCC, highlighting its potential as a therapeutic target in the future.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0