Oncogene最新文献_第9页

A safe haven for cancer cells: tumor plus stroma control by DYRK1B

IF 6.9 1区医学

Oncogene Pub Date : 2025-01-25 DOI: 10.1038/s41388-025-03275-6

Miriam Ems, Anna Brichkina, Matthias Lauth

{"title":"A safe haven for cancer cells: tumor plus stroma control by DYRK1B","authors":"Miriam Ems, Anna Brichkina, Matthias Lauth","doi":"10.1038/s41388-025-03275-6","DOIUrl":"10.1038/s41388-025-03275-6","url":null,"abstract":"The development of resistance remains one of the biggest challenges in clinical cancer patient care and it comprises all treatment modalities from chemotherapy to targeted or immune therapy. In solid malignancies, drug resistance is the result of adaptive processes occurring in cancer cells or the surrounding tumor microenvironment (TME). Future therapy attempts will therefore benefit from targeting both, tumor and stroma compartments and drug targets which affect both sides will be highly appreciated. In this review, we describe a seemingly paradoxical oncogenic mediator with this potential: The dual-specificity tyrosine-phosphorylation regulated kinase 1B (DYRK1B). DYRK1B promotes proliferative quiescence and yet is overexpressed or amplified in many hyperproliferative malignancies including ovarian cancer and pancreatic cancer. In particular the latter disease is a paradigmatic example for a therapy-recalcitrant and highly stroma-rich cancer entity. Here, recent evidence suggests that DYRK1B exerts its oncogenic features by installing a protective niche for cancer cells by directly affecting cancer cells but also the TME. Specifically, DYRK1B not only fosters cell-intrinsic processes like cell survival, chemoresistance, and disease recurrence, but it also upregulates TME and cancer cell-protective innate immune checkpoints and down-modulates anti-tumoral macrophage functionality. In this article, we outline the well-established cell-autonomous roles of DYRK1B and extend its importance to the TME and the control of the tumor immune stroma. In summary, DYRK1B appears as a single novel key player creating a safe haven for cancer cells by acting cell-intrinsically and—extrinsically, leading to the promotion of cancer cell survival, chemoresistance, and relapse. Thus, DYRK1B appears as an attractive drug target for future therapeutic approaches.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 6","pages":"341-347"},"PeriodicalIF":6.9,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-025-03275-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040620","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

S100A8/A9 innate immune signaling as a distinct mechanism driving progression of smoking-related breast cancers.

IF 6.9 1区医学

Oncogene Pub Date : 2025-01-25 DOI: 10.1038/s41388-025-03276-5

Samson Mugisha, Shahnawaz A Baba, Shreyas Labhsetwar, Devam Dave, Aran Zakeri, Richard Klemke, Jay S Desgrosellier

{"title":"S100A8/A9 innate immune signaling as a distinct mechanism driving progression of smoking-related breast cancers.","authors":"Samson Mugisha, Shahnawaz A Baba, Shreyas Labhsetwar, Devam Dave, Aran Zakeri, Richard Klemke, Jay S Desgrosellier","doi":"10.1038/s41388-025-03276-5","DOIUrl":"https://doi.org/10.1038/s41388-025-03276-5","url":null,"abstract":"Smoking plays an underappreciated role in breast cancer progression, increasing recurrence and mortality in patients. Here, we show that S100A8/A9 innate immune signaling is a molecular mechanism that identifies smoking-related breast cancers and underlies their enhanced malignancy. In contrast to acute exposure, chronic nicotine increased tumorigenicity and reprogrammed breast cancer cells to express innate immune response genes. This required the α7 nicotinic acetylcholine receptor, which elicited dynamic changes in cell differentiation, proliferation, and expression of secreted cytokines, such as S100A8 and S100A9, as assessed by unbiased scRNA-seq. Indeed, pharmacologic or genetic inhibition of S100A8/A9-RAGE receptor signaling blocked nicotine's tumor-promoting effects. We also discovered Syntaphilin (SNPH) as an S100A8/A9-dependent gene enriched specifically in estrogen receptor-negative (ER-) cancers from former smokers, linking this response to patient disease. Together, our findings describe a new α7 nAChR-S100A8/A9-Syntaphilin immune signaling module that drives nicotine-induced tumor progression and distinguishes smoking-related patient disease as a distinct subset of aggressive breast cancers.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040622","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

Finding a needle in a haystack: functional screening for novel targets in cancer immunology and immunotherapies

IF 6.9 1区医学

Oncogene Pub Date : 2025-01-25 DOI: 10.1038/s41388-025-03273-8

Yi Du, Yang Yang, Bohao Zheng, Qian Zhang, Shengtao Zhou, Linjie Zhao

{"title":"Finding a needle in a haystack: functional screening for novel targets in cancer immunology and immunotherapies","authors":"Yi Du, Yang Yang, Bohao Zheng, Qian Zhang, Shengtao Zhou, Linjie Zhao","doi":"10.1038/s41388-025-03273-8","DOIUrl":"10.1038/s41388-025-03273-8","url":null,"abstract":"Genome-wide functional genetic screening has been widely used in the biomedicine field, which makes it possible to find a needle in a haystack at the genetic level. In cancer research, gene mutations are closely related to tumor development, metastasis, and recurrence, and the use of state-of-the-art powerful screening technologies, such as clustered regularly interspaced short palindromic repeat (CRISPR), to search for the most critical genes or coding products provides us with a new possibility to further refine the cancer mapping and provide new possibilities for the treatment of cancer patients. The use of CRISPR screening for the most critical genes or coding products has further refined the cancer atlas and provided new possibilities for the treatment of cancer patients. Immunotherapy, as a highly promising cancer treatment method, has been widely validated in the clinic, but it could only meet the needs of a small proportion of cancer patients. Finding new immunotherapy targets is the key to the future of tumor immunotherapy. Here, we revisit the application of functional screening in cancer immunology from different perspectives, from the selection of diverse in vitro and in vivo screening models to the screening of potential immune checkpoints and potentiating genes for CAR-T cells. The data will offer fresh therapeutic clues for cancer patients.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 7","pages":"409-426"},"PeriodicalIF":6.9,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-025-03273-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040621","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

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":"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":"44 14","pages":"983-995"},"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

{"title":"m6A-modified circSTX6 as a key regulator of cervical cancer malignancy via SPI1 and IL6/JAK2/STAT3 pathways","authors":"Xiaotian Han, Lingfang Xia, Yong Wu, Xiaojun Chen, Xiaohua Wu","doi":"10.1038/s41388-024-03260-5","DOIUrl":"10.1038/s41388-024-03260-5","url":null,"abstract":"In recent years, circRNAs have garnered increasing attention for their role in cervical cancer. However, the functions of many newly identified circRNAs remain unclear and require further exploration. In this study, we investigated the expression and oncogenic potential of the novel circRNA circSTX6 in cervical cancer. Our findings revealed that circSTX6 is highly expressed in cervical cancer (CC) and is significantly associated with poor patient prognosis, promoting cell survival, proliferation, invasion, and migration. Mechanistically, circSTX6 enhances the stability of the transcription factor SPI1 by binding to it, thereby upregulating IL6 transcription and activating the JAK2/STAT3 signaling pathway. Additionally, METTL3-mediated N6-methyladenosine (m6A) modification stabilizes circSTX6 through recognition by YTHDC1, forming a positive feedback regulatory loop among METTL3, circSTX6, and SPI1. These findings not only deepen our understanding of the biological mechanisms underlying CC but also highlight circSTX6 as a potential target for molecular therapies.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 14","pages":"968-982"},"PeriodicalIF":6.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-024-03260-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008936","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