Oncogene最新文献

{"title":"Immunomodulatory function of cannabinoid receptor 2 and its agonist osteogenic growth peptide in health and cancer: a study in mice and humans","authors":"Jennifer Ana Iden, Nathalie Ben-Califa, Aaron Naim, Tamar Liron, Drorit Neumann, Yankel Gabet","doi":"10.1038/s41388-025-03399-9","DOIUrl":"10.1038/s41388-025-03399-9","url":null,"abstract":"Colon carcinoma is among the most prevalent malignant tumors, with inflammation being the primary risk factor. Cannabinoid receptor 2 (CB2/CNR2) has complex immunomodulatory functions. Therefore, we investigated the role of osteogenic growth peptide (OGP), an endogenous selective CB2 agonist, in colon carcinogenesis and immune modulation in transgenic mice (ApcMin/+).We injected 8-week-old (progression phase) or five-week-old (initiation phase) ApcMin/+ mice with OGP or vehicle weekly for 8 weeks or 4 weeks, respectively. During the progression phase, OGP-treated mice displayed significantly fewer tumors in the large intestine and smaller tumors in the small intestine. During the initiation phase, OGP significantly attenuated adenomagenesis in both the small and large intestine, decreased IL-6 and IL-4 levels, increased splenic anti-tumor CD8+ T cells, and diminished populations of tumor-promoting myeloid-derived suppressor cells. Further, we used exomic analyses of UKBiobank patients to determine the relationship between CNR2 polymorphisms and tumor-associated myeloid cells in humans. We found that the common CNR2-Q63R polymorphism is associated with monocyte count. Our results suggest that CB2 activation via OGP attenuates tumorigenesis and adenoma growth by modulating immune cells, corroborated by a significant association between CNR2 polymorphisms and monocytopoiesis in humans.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 29","pages":"2504-2514"},"PeriodicalIF":6.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-025-03399-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040289","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}

{"title":"A targeted literature review on the impact of tailored interventions on patient outcomes in oncology","authors":"Graham Ferrier, Aleksandra Filipovic, Harpreet Wasan, Alessandra di Pietro, Deepali Mittal, Geetanjali Kamath, Saifuddin Kharawala, Faisal Mehmud","doi":"10.1038/s41388-025-03424-x","DOIUrl":"10.1038/s41388-025-03424-x","url":null,"abstract":"Non-pharmacological approaches to managing symptoms and side effects of cancer treatments are not always aligned with true needs and characteristics of patients. Without proactive patient-tailored interventions to anticipate, prevent, and manage side effects, risk of patients experiencing treatment interruption or discontinuation increases. A targeted literature review identified published studies evaluating the impact of tailored (customized based on individual patient characteristics) non-pharmacological interventions on patient outcomes in oncology versus routine care (usual clinical practice), enhanced care (support beyond routine care, including additional patient education, psychological support, and medication tracking), or uniform engagement (non-tailored support offered in a uniform manner). Thirty completed clinical studies were included. Approximately 50% of interventions across studies were remote health education/self-management programs, and the remaining provided clinical follow-up for symptom management. All types of tailored intervention led to positive patient outcomes versus routine care. Significant improvements were seen in favor of self-efficacy for self-management (patient’s belief in their ability to manage own symptoms and treatment; p < 0.05) and symptom burden (overall as well as specific symptoms including anxiety, nausea, vomiting; all p < 0.05), although there were inconsistent effects on health-related quality of life (HRQoL), healthcare resource utilization (HCRU), and adherence. Compared with enhanced care, most studies showed no consistent improvement for tailored interventions in symptom burden, self-efficacy, HRQoL, HCRU or adherence, although benefits were slightly more common in larger/longer studies. Tailored interventions were not consistently better than uniform engagement in improving outcomes, although the number of studies was limited, with small sample sizes/short follow-ups. In summary, tailored interventions showed positive benefits versus routine or enhanced care (the latter only in larger and longer studies). No consistent benefit was observed compared with uniform engagement. Clinical outcomes were most sensitive to type of intervention. Tools to both enhance and measure the process should be routinely incorporated in clinical trials.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 20","pages":"1439-1451"},"PeriodicalIF":6.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-025-03424-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939698","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}

{"title":"β-Catenin interacts with canonical RBPs including MSI2 to associate with a Wnt signalling mRNA network in myeloid leukaemia cells","authors":"M. Wagstaff, O. Sevim, A. Goff, M. Raynor, H. Park, E. J. Mancini, D. T. T. Nguyen, T. Chevassut, A. Blair, L. Castellano, S. Newbury, B. Towler, R. G. Morgan","doi":"10.1038/s41388-025-03415-y","DOIUrl":"10.1038/s41388-025-03415-y","url":null,"abstract":"Wnt/β-catenin signalling is important for normal hematopoietic stem/progenitor cell (HSPC) biology and heavily implicated in acute and chronic myeloid leukaemia (AML and CML). The central mediator β-catenin is an attractive therapeutic target in myeloid neoplasms however its targeting has been hampered by a poor characterisation of its molecular interactions in haematopoietic cells, which will differ from its network in solid tissues. Our previous β-catenin interactome study identified the significant enrichment of RNA-binding proteins (RBP) implying post-transcriptional roles for β-catenin in myeloid cells. To identify β-catenin interacting mRNAs we performed β-catenin RNA-immunoprecipitation coupled to RNA-sequencing (RIP-seq) and identified significantly enriched Wnt signalling pathway transcripts. Using β-catenin cross-linking immunoprecipitation (CLIP) we demonstrated a limited capacity for β-catenin to bind RNA directly, implying dependence on other RBPs. β-Catenin was found to interact with Musashi-2 (MSI2) in both myeloid cell lines and primary AML patient samples, where expression was significantly correlated. MSI2 knockdown reduced Wnt signalling output (TCF/LEF activity), through suppression of LEF-1 expression and nuclear localisation. Through both RIP and CLIP we demonstrate MSI2 binds LEF1 mRNA in a partly β-catenin dependent fashion, and may impact the post-transcriptional control of LEF-1 expression. Finally, we show that MSI2-mediated expansion of human HSPCs could be partly driven through LEF1 regulation. This is the first study to experimentally demonstrate functional crosstalk between MSI2 and Wnt signalling in human cells, and indicates potential novel post-transcriptional roles for β-catenin in a haematological context.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 29","pages":"2490-2503"},"PeriodicalIF":6.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-025-03415-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038937","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}

{"title":"SETD5 facilitates stemness and represses ferroptosis via m6A-mediating PKM2 stabilization in non-small cell lung cancer","authors":"Xingzhe Liu, Yuzhen Cui, Jie Gong, Xinhui Yu, Yan Cui, Yanhua Xuan","doi":"10.1038/s41388-025-03426-9","DOIUrl":"10.1038/s41388-025-03426-9","url":null,"abstract":"SETD5, an atypical member of the histone lysine methyltransferase family known for its association with cancer stemness, is a significant predictor of unfavorable survival outcomes in non-small cell lung cancer (NSCLC). However, the function of SETD5 in NSCLC stemness remains unclear, and whether it is an active H3K36me3 is controversial. Consequently, further investigation is required to clarify the pivotal role of SETD5 in NSCLC stemness and its related mechanism. Thus, this study employed the NSCLC tissue microarray and bioinformatics tools to analyze SETD5 expression and determine its effect on stemness and investigated the role of SETD5 in the metastasis of NSCLC using in vitro and in vivo analyses. The findings indicated high SETD5 expression in embryonic and NSCLC tissues, which was related to the pathological tumor stage, lymph node metastasis, and clinical stage, indicating that SETD5 could be used as a biomarker and prognostic factor in NSCLC. In addition, we found that SETD5 can promote glycolysis, thereby inhibiting ferroptosis and promoting the stemness of NSCLC, causing tumor metastasis and adverse prognosis in patients. In terms of mechanism, SETD5 as H3K36me3 facilitates the m6A modification of METTL14 and the recruitment of YTHDF1 and mediates PKM2 nuclear translocation and phosphorylation of p-PKM2 Tyr105, regulating GPX4 mediated ferroptosis resistance and SOX9 mediated stemness in NSCLC. The findings emphasize that SETD5 may serve as a promising indicator of stemness in NSCLC, which can help develop therapeutic targets for NSCLC and prognostic evaluation.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 29","pages":"2474-2489"},"PeriodicalIF":6.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-025-03426-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033870","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}

{"title":"Retraction Note to: RNAi-mediated inhibition of cathepsin B and uPAR leads to decreased cell invasion, angiogenesis and tumor growth in gliomas","authors":"Christopher S. Gondi, Sajani S. Lakka, Dzung H. Dinh, William C. Olivero, Meena Gujrati, Jasti S. Rao","doi":"10.1038/s41388-025-03403-2","DOIUrl":"10.1038/s41388-025-03403-2","url":null,"abstract":"","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 20","pages":"1548-1548"},"PeriodicalIF":6.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-025-03403-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939684","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}

{"title":"Primary cilia and cancer: a tale of many faces","authors":"Rebecca Collinson, Barbara Tanos","doi":"10.1038/s41388-025-03416-x","DOIUrl":"10.1038/s41388-025-03416-x","url":null,"abstract":"Cilia are microtubule-based sensory organelles which project from the cell surface, enabling detection of mechanical and chemical stimuli from the extracellular environment. It has been shown that cilia are lost in some cancers, while others depend on cilia or ciliary signaling. Several oncogenic molecules, including tyrosine kinases, G-protein coupled receptors, cytosolic kinases, and their downstream effectors localize to cilia. The Hedgehog pathway, one of the most studied ciliary-signaling pathways, is regulated at the cilium via an interplay between Smoothened (an oncogene) and Patched (a tumor suppressor), resulting in the activation of pro-survival programs. Interestingly, cilia loss can result in resistance to Smoothened-targeting drugs and increased cancer cell survival. On the other hand, kinase inhibitor-resistant and chemoresistant cancers have increased cilia and increased Hedgehog pathway activation, and suppressing cilia can overcome this resistance. How cilia regulate cancer is therefore context dependent. Defining the signaling output of cilia-localized oncogenic pathways could identify specific targets for cancer therapy, including the cilium itself. Increasing evidence implicates cilia in supporting several hallmarks of cancer, including migration, invasion, and metabolic rewiring. While cell cycle cues regulate the biogenesis of cilia, the absence of cilia has not been conclusively shown to affect the cell cycle. Thus, a complex interplay between molecular signals, phosphorylation events and spatial regulation renders this fascinating organelle an important new player in cancer through roles that we are only starting to uncover. In this review, we discuss recent advances in our understanding of cilia as signaling platforms in cancer and the influence this plays in tumor development.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 21","pages":"1551-1566"},"PeriodicalIF":6.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-025-03416-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997074","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}

{"title":"Retraction Note: Inhibition of cathepsin B and MMP-9 gene expression in glioblastoma cell line via RNA interference reduces tumor cell invasion, tumor growth and angiogenesis","authors":"Sajani S. Lakka, Christopher S. Gondi, Niranjan Yanamandra, William C. Olivero, Dzung H. Dinh, Meena Gujrati, Jasti S. Rao","doi":"10.1038/s41388-025-03402-3","DOIUrl":"10.1038/s41388-025-03402-3","url":null,"abstract":"","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 20","pages":"1549-1549"},"PeriodicalIF":6.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-025-03402-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939685","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}

{"title":"CLDN18.2-targeting STAR-T cell therapy for pancreatic cancer: a strategy to minimize gastric off-tumor toxicity compared to CLDN18.2 CAR-T","authors":"Wei Zhang, Miao Zeng, Xingyu Ma, Jinghong Chen, Jingqiao Qiao, Ziqian He, Guocheng Zhong, Yisheng Li, Li Yu","doi":"10.1038/s41388-025-03414-z","DOIUrl":"10.1038/s41388-025-03414-z","url":null,"abstract":"Claudin18 isoform 2 (CLDN18.2), primarily expressed in gastric tissue and upregulated in pancreatic cancer (PC), is a key target for innovative treatments like chimeric antigen receptor T (CAR-T) cell therapy. However, CAR-T’s effectiveness comes with a significant risk of on-target, off-tumor (OTOT) toxicity due to CLDN18.2’s presence in normal gastric mucosa. To address this, we developed CLDN18.2-specific synthetic T cell receptor and antigen receptor T (STAR-T) cells. Our research shows that STAR-T and CAR-T cells have comparable in vitro cytotoxicity, but STAR-T cells cause less gastric damage in vivo despite having weaker antitumor effects than CAR-T cells. Clinical tests with gastroscopes confirmed the gastric safety of STAR-T cell therapy, which effectively controlled the disease. Additionally, incorporating the IL12β p40 subunit into STAR-T cells enhanced their function in both lab and animal studies. This evidence suggests that CLDN18.2 STAR-T cell could be a safer alternative to CAR-T cell therapy for PC, meriting further clinical trials.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 28","pages":"2440-2452"},"PeriodicalIF":6.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025587","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}

{"title":"A novel role for Neurog2 in MYCN driven neuroendocrine plasticity of prostate cancer","authors":"Prachi Walke, Jared D. W. Price, Frederick S. Vizeacoumar, Nickson Joseph, Vincent Maranda, Bari Chowdhury, Jay Patel, Yue Zhang, He Dong, Lara New, Ashtalakshmi Ganapathysamy, Li Hui Gong, Mary Lazell-Wright, Hussain Elhasasna, Kalpana K. Bhanumathy, Yuliang Wu, Yuzhuo Wang, Andrew Freywald, Anand Krishnan, Franco J. Vizeacoumar","doi":"10.1038/s41388-025-03413-0","DOIUrl":"10.1038/s41388-025-03413-0","url":null,"abstract":"Neuroendocrine prostate cancer (NEPC) presents a formidable clinical challenge owing to its aggressive progression and resistance to conventional therapies. A key driver of NEPC is the overexpression of MYCN, a well-established oncogene associated with neuroendocrine tumors. However, efforts to directly inhibit the N-Myc protein encoded by this gene have resulted in limited success, thereby hindering therapeutic advancements. To overcome this obstacle, we conducted unbiased genome-wide screening using isogenic prostate cancer cell lines to identify the synthetic vulnerabilities of MYCN. Among the identified candidates, NEUROG2 emerged as a significant candidate. Neurog2 is a proneural transcription factor (PTF) known for its role in developmental processes and trans-differentiation of adult cells. Our findings demonstrate that Neurog2 depletion does not affect non-malignant cells but significantly suppresses the growth of MYCN-overexpressing cells and tumors in orthotopic NEPC models. Furthermore, our observations indicate that Neurog2-driven modulation of PTFs potentially contribute to NEPC development. Thus, targeting Neurog2 holds promise as an effective therapeutic strategy for MYCN-overexpressing NEPC.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 29","pages":"2460-2473"},"PeriodicalIF":6.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-025-03413-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038926","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}

{"title":"Retraction Note: Downregulation of MMP-9 in ERK-mutated stable transfectants inhibits glioma invasion in vitro","authors":"Sajani S. Lakka, Sushma L. Jasti, Christopher Gondi, Douglas Boyd, Nirmala Chandrasekar, Dzung H. Dinh, William C. Olivero, Meena Gujrati, Jasti S. Rao","doi":"10.1038/s41388-025-03397-x","DOIUrl":"10.1038/s41388-025-03397-x","url":null,"abstract":"","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"44 20","pages":"1547-1547"},"PeriodicalIF":6.9,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41388-025-03397-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939696","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}