Oncogene最新文献

Correction: p73 and caspase-cleaved p73 fragments localize to mitochondria and augment TRAIL-induced apoptosis.

IF 6.9 1区医学

Oncogene Pub Date : 2025-01-22 DOI: 10.1038/s41388-024-03256-1

A E Sayan, B S Sayan, V Gogvadze, D Dinsdale, U Nyman, T M Hansen, B Zhivotovsky, G M Cohen, R A Knight, G Melino

引用次数: 0

Correction: USP10 drives cancer stemness and enables super-competitor signalling in colorectal cancer.

IF 6.9 1区医学

Oncogene Pub Date : 2025-01-22 DOI: 10.1038/s41388-024-03262-3

Michaela Reissland, Oliver Hartmann, Saskia Tauch, Jeroen M Bugter, Cristian Prieto-Garcia, Clemens Schulte, Sinah Loebbert, Daniel Solvie, Eliya Bitman-Lotan, Ashwin Narain, Anne-Claire Jacomin, Christina Schuelein-Voelk, Carmina T Fuss, Nikolett Pahor, Carsten Ade, Viktoria Buck, Michael Potente, Vivian Li, Gerti Beliu, Armin Wiegering, Tom Grossmann, Martin Eilers, Elmar Wolf, Hans Maric, Mathias Rosenfeldt, Madelon M Maurice, Ivan Dikic, Peter Gallant, Amir Orian, Markus E Diefenbacher

引用次数: 0

Correction: BEX4 inhibits the progression of clear cell renal cell carcinoma by stabilizing SH2D4A, which is achieved by blocking SIRT2 activity.

IF 6.9 1区医学

Oncogene Pub Date : 2025-01-22 DOI: 10.1038/s41388-025-03278-3

Ziyao Li, Shiyong Xin, Liqun Huang, Ye Tian, Weihua Chen, Xiang Liu, Bowen Ye, Rong Bai, Guosheng Yang, Wenwen Wang, Lin Ye

引用次数: 0

Evidence of DNA methylation heterogeneity and epipolymorphism in kidney cancer tissue samples. 肾癌组织样本中DNA甲基化异质性和表观多态性的证据。

IF 6.9 1区医学

Oncogene Pub Date : 2025-01-17 DOI: 10.1038/s41388-024-03270-3

Sabrina H Rossi, Victoria Dombrowe, Laura Godfrey, Teodora Bucaciuc Mracica, Sara Pita, Toby Milne-Clark, Justicia Kyeremeh, Gahee Park, Christopher G Smith, Radoslaw P Lach, Anne Babbage, Anne Y Warren, Thomas J Mitchell, Grant D Stewart, Roland Schwarz, Charlie E Massie

{"title":"Evidence of DNA methylation heterogeneity and epipolymorphism in kidney cancer tissue samples.","authors":"Sabrina H Rossi, Victoria Dombrowe, Laura Godfrey, Teodora Bucaciuc Mracica, Sara Pita, Toby Milne-Clark, Justicia Kyeremeh, Gahee Park, Christopher G Smith, Radoslaw P Lach, Anne Babbage, Anne Y Warren, Thomas J Mitchell, Grant D Stewart, Roland Schwarz, Charlie E Massie","doi":"10.1038/s41388-024-03270-3","DOIUrl":"https://doi.org/10.1038/s41388-024-03270-3","url":null,"abstract":"Clear cell renal cell carcinoma (ccRCC) is characterised by significant genetic heterogeneity, which has diagnostic and prognostic implications. Very limited evidence is available regarding DNA methylation heterogeneity. We therefore generate sequence level DNA methylation data on 136 multi-region tumour and normal kidney tissue from 18 ccRCC patients, along with matched whole exome sequencing (85 samples) and gene expression (47 samples) data on a subset of samples. We perform a comprehensive systematic analysis of heterogeneity between patients, within a patient and within a sample. We demonstrate that bulk methylation data may be deconvoluted into cell-type-specific latent methylation components (LMCs), and that LMC1, which is likely to represent T cells, is associated with prognostic parameters. Differential epipolymorphism was noted between ccRCC and normal tissue in the promoter region of genes which are known to be associated with kidney cancer. This was externally validated in an independent cohort of 71 ccRCC and normal kidney tissues. Differential epipolymorphism in the gene promoter was a predictor of gene expression, after adjusting for average methylation. This represents the first evaluation of epipolymorphism in ccRCC and suggests that gains and losses in methylation disorder may have a functional relevance, gleaning important information on tumourigenesis.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008923","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

Oncogenic potential of truncated-Gli3 via the Gsk3β/Gli3/AR-V7 axis in castration-resistant prostate cancer. 截断Gli3通过Gsk3β/Gli3/AR-V7轴在去势抵抗性前列腺癌中的致癌潜力

IF 6.9 1区医学

Oncogene Pub Date : 2025-01-16 DOI: 10.1038/s41388-024-03266-z

Jyoti B Kaushal, Pratima Raut, Sushanta Halder, Zahraa W Alsafwani, Seema Parte, Gunjan Sharma, K M Abdullah, Parthasarathy Seshacharyulu, Subodh M Lele, Surinder K Batra, Jawed A Siddiqui

{"title":"Oncogenic potential of truncated-Gli3 via the Gsk3β/Gli3/AR-V7 axis in castration-resistant prostate cancer.","authors":"Jyoti B Kaushal, Pratima Raut, Sushanta Halder, Zahraa W Alsafwani, Seema Parte, Gunjan Sharma, K M Abdullah, Parthasarathy Seshacharyulu, Subodh M Lele, Surinder K Batra, Jawed A Siddiqui","doi":"10.1038/s41388-024-03266-z","DOIUrl":"10.1038/s41388-024-03266-z","url":null,"abstract":"The functional activation of the androgen receptor (AR) and its interplay with the aberrant Hh/Gli cascade are pivotal in the progression of castration-resistant prostate cancer (CRPC) and resistance to AR-targeted therapies. Our study unveiled a novel role of the truncated form of Gli (t-Gli3) in advancing CRPC. Investigation into Gli3 regulation revealed a Smo-independent mechanism for its activation. Despite lacking a transactivation domain, t-Gli3 relies on androgen receptor variant 7 (AR-V7) for its action. Mechanistically, Gsk3β activation led to the t-Gli3 generation, and inhibition of Gsk3β supported the accumulation of full-length Gli3 expression through a non-canonical mechanism. Knockdown of Gsk3β (Gsk3β KD) reduces CRPC cell proliferation, induces apoptosis via mitochondrial fragmentation, and triggers metabolomic reprogramming. The in vivo studies with Gsk3β KD cells in the mouse prostate resulted in tumor growth retardation compared to scramble cells. RNA-seq HALLMARK Gene Set Enrichment Analysis (GSEA) analysis of Gsk3β KD revealed a positive enrichment of apoptosis, tumor suppressor gene, and negative enrichment of oncogenic pathway. Furthermore, combinational use of a Gsk3β inhibitor with anti-Smo or Gli1 significantly inhibited the CRPC cell growth, which is resistant to individual Smo or Gli1 inhibitor targeting. Intriguingly, solely targeting Gli3 showed effectiveness in inhibiting CRPC cell growth. Overall, our study underscores the clinical significance of Gli3, emphasizing t-Gli3, and provides novel insights into the interplay of the Gsk3β/t-Gli3/AR-V7 axis in CRPC.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009118","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

Pyrithione zinc alters mismatch repair to trigger tumor immunogenicity. 吡硫酮锌改变错配修复触发肿瘤免疫原性。

IF 6.9 1区医学

Oncogene Pub Date : 2025-01-15 DOI: 10.1038/s41388-024-03272-1

Huanling Zhang, Jiaxin Wu, Lei Cui, Tiantian Wang, Huan Jin, Hui Guo, Chunyuan Xie, Lin Li, Xiaojuan Wang, Zining Wang

{"title":"Pyrithione zinc alters mismatch repair to trigger tumor immunogenicity.","authors":"Huanling Zhang, Jiaxin Wu, Lei Cui, Tiantian Wang, Huan Jin, Hui Guo, Chunyuan Xie, Lin Li, Xiaojuan Wang, Zining Wang","doi":"10.1038/s41388-024-03272-1","DOIUrl":"https://doi.org/10.1038/s41388-024-03272-1","url":null,"abstract":"Mismatch repair deficiency (dMMR) cancers are highly sensitive to immunotherapy, but only account for a small fraction of cancer patients. How to increase immunotherapy efficacy on MMR-proficient (pMMR) cancer is still a major challenge. This study demonstrates that pyrithione zinc (PYZ), an FDA-approved drug, can enhance tumor immunogenicity via altering MMR and activating STING signaling. Mechanistically, PYZ elevates levels of ROS, leading to the upregulation of HIF-1α and DNA damage, while also inhibiting the expression of DNA mismatch repair proteins MSH2 and MSH6, together promoting DNA damage accumulation. Therefore, the administration of PYZ results in the accumulation of DNA damage, leading to the activation of STING signaling, which enhances tumor immunogenicity. Knockout of Sting diminishes the activation of IFN-I signaling induced by PYZ and reduces tumor immunogenicity. Furthermore, in vivo administration of PYZ promotes the infiltration of CD8+ T cells into the tumor and inhibits tumor growth, an effect that is attenuated in Nude mice or mice with CD8+ T cell depletion or deficiency of Ifnar. Overall, our findings showed that pyrithione zinc could trigger tumor immunogenicity by downregulating MMR machinery and activating STING pathway in tumor cells, and provide a translational approach to improve immunotherapy on pMMR cancer.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009120","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

m6A-modified circSTX6 as a key regulator of cervical cancer malignancy via SPI1 and IL6/JAK2/STAT3 pathways. m6a修饰的circSTX6通过SPI1和IL6/JAK2/STAT3通路作为宫颈癌恶性的关键调节因子。

IF 6.9 1区医学

Oncogene Pub Date : 2025-01-15 DOI: 10.1038/s41388-024-03260-5

Xiaotian Han, Lingfang Xia, Yong Wu, Xiaojun Chen, Xiaohua Wu

引用次数: 0

Global profiling of alternative splicing in non-small cell lung cancer reveals novel histological and population differences. 非小细胞肺癌中选择性剪接的全球分析揭示了新的组织学和人群差异。

IF 6.9 1区医学

Oncogene Pub Date : 2025-01-10 DOI: 10.1038/s41388-024-03267-y

Saman Zeeshan, Bhavik Dalal, Rony F Arauz, Adriana Zingone, Curtis C Harris, Hossein Khiabanian, Sharon R Pine, Bríd M Ryan

{"title":"Global profiling of alternative splicing in non-small cell lung cancer reveals novel histological and population differences.","authors":"Saman Zeeshan, Bhavik Dalal, Rony F Arauz, Adriana Zingone, Curtis C Harris, Hossein Khiabanian, Sharon R Pine, Bríd M Ryan","doi":"10.1038/s41388-024-03267-y","DOIUrl":"10.1038/s41388-024-03267-y","url":null,"abstract":"Lung cancer is one of the most frequently diagnosed cancers in the US. African-American (AA) men are more likely to develop lung cancer with higher incidence and mortality rates than European-American (EA) men. Herein, we report high-confidence alternative splicing (AS) events from high-throughput, high-depth total RNA sequencing of lung tumors and non-tumor adjacent tissues (NATs) in two independent cohorts of patients with adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). We identified novel AS biomarkers with notable differential percent spliced in (PSI) values between lung tumors and NATs enriched in the AA and EA populations, which were associated with oncogenic signaling pathways. We also uncovered tumor subtype- and population-specific AS events associated with cell surface proteins and cancer driver genes. We highlighted significant AS events in SYNE2 specific to LUAD in both populations, as well as those in CD44 from EAs and TMBIM6 from AAs specific to LUAD. Here, we also present the validation of cancer signatures based on direct high-throughput reverse transcription-PCR. Our large survey of lung tumors presents a rich data resource that may help to understand molecular subtypes of lung tumor between AAs and EAs and reveal new therapeutic vulnerabilities that potentially advance health equity.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952150","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

Retraction Note: Exosomal miR-4466 from nicotine-activated neutrophils promotes tumor cell stemness and metabolism in lung cancer metastasis. 注：尼古丁激活的中性粒细胞外泌体miR-4466在肺癌转移过程中促进肿瘤细胞的干细胞性和代谢。

IF 6.9 1区医学

Oncogene Pub Date : 2025-01-09 DOI: 10.1038/s41388-024-03269-w

Abhishek Tyagi, Shih-Ying Wu, Sambad Sharma, Kerui Wu, Dan Zhao, Ravindra Deshpande, Ravi Singh, Wencheng Li, Umit Topaloglu, Jimmy Ruiz, Kounosuke Watabe

引用次数: 0

Mevalonate kinase inhibits anti-tumor immunity by impairing the tumor cell-intrinsic interferon response in microsatellite instability colorectal cancer. 甲羟戊酸激酶在微卫星不稳定性结直肠癌中通过损害肿瘤细胞内源干扰素应答抑制抗肿瘤免疫。

IF 6.9 1区医学

Oncogene Pub Date : 2024-12-26 DOI: 10.1038/s41388-024-03255-2

Yuanyu Liao, Rui Yang, Bojun Wang, Yuli Ruan, Luying Cui, Jiani Yang, Xuefan Yu, Shuling Han, Yuanfei Yao, Xindi Luan, Yingjue Li, Mengde Shi, Shuijie Li, Chao Liu, Yanqiao Zhang

{"title":"Mevalonate kinase inhibits anti-tumor immunity by impairing the tumor cell-intrinsic interferon response in microsatellite instability colorectal cancer.","authors":"Yuanyu Liao, Rui Yang, Bojun Wang, Yuli Ruan, Luying Cui, Jiani Yang, Xuefan Yu, Shuling Han, Yuanfei Yao, Xindi Luan, Yingjue Li, Mengde Shi, Shuijie Li, Chao Liu, Yanqiao Zhang","doi":"10.1038/s41388-024-03255-2","DOIUrl":"https://doi.org/10.1038/s41388-024-03255-2","url":null,"abstract":"Insufficient tumor cell-intrinsic interferon response represents a major obstacle in immune checkpoint blockade (ICB) therapy, particularly in anti-PD-1 treatment. Although cholesterol metabolism has been demonstrated to be a critical regulator of anti-tumor immune responses, whether cholesterol influences tumor cell-intrinsic interferon response in microsatellite instability (MSI) colorectal cancer (CRC) remains unknown. Through comprehensive siRNA library screening and Gene Set Enrichment Analysis (GSEA), we identified mevalonate kinase (MVK) as a crucial negative regulator of tumor cell-intrinsic interferon response in MSI CRC cells. Genetic ablation of MVK resulted in significant upregulation of Th1 type chemokines (CXCL9 and CXCL10) and enhanced CD8+T cell infiltration in MSI CRC, consequently leading to marked tumor growth suppression in immunocompetent mice. At the molecular level, we demonstrated that MVK physically interacts with the transcriptional activation domain (TAD) of signal transducer and activator of transcription 1 (STAT1). This interaction substantially impairs STAT1 nuclear translocation, thereby attenuating interferon signaling cascade. Furthermore, analyses of humanized PBMC-PDX models and clinical cohorts of MSI CRC patients revealed that reduced MVK expression in tumor tissues strongly correlates with favorable responses to anti-PD-1 therapy. Collectively, our findings establish MVK as a pivotal mediator in cholesterol synthesis pathway that negatively regulates tumor cell-intrinsic interferon response in MSI CRC. These results suggest that therapeutic targeting of MVK represents a promising strategy to enhance ICB efficacy through potentiation of interferon responses in MSI CRC patients.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896508","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