Neoplasia最新文献

{"title":"MYC alterations in multiple myeloma: Genetic insights and prognostic impact","authors":"Sara Cristóbal-Vargas ,&nbsp;Myriam Cuadrado ,&nbsp;Norma C Gutiérrez","doi":"10.1016/j.neo.2025.101177","DOIUrl":"10.1016/j.neo.2025.101177","url":null,"abstract":"<div><div>Multiple myeloma (MM) is a hematologic malignancy with high genetic complexity. The genetic alterations that drive MM have classically been classified as primary abnormalities, including <em>IGH</em> translocations and hyperdiploidy, and secondary abnormalities, mainly composed of 1q gains, 17p deletions and <em>MYC</em> rearrangements. Dysregulation of the <em>MYC</em> oncogene has been proposed as a key factor in disease progression from monoclonal gammopathy of undetermined significance (MGUS), smoldering MM and overt MM. <em>MYC</em>, a multifunctional transcription factor, is frequently activated in MM through various mechanisms, including translocations, amplifications, and overexpression, thereby contributing to the growth and survival of malignant plasma cells. The role of <em>MYC</em> abnormalities in the prognosis of MM remains controversial and continues to be overlooked in current prognostic indices for MM. The different methodologies used to detect <em>MYC</em> lesions may hinder the interpretation of the apparently contradictory results between studies analyzing the impact of these alterations on the survival of MM patients. On the other hand, the mouse models that best mimic the characteristics of human MM are those driven by <em>MYC</em>.</div><div>In this review, we provide an overview of the <em>MYC</em> alterations described in MM, indicating the methodologies used to detect them and discussing their influence on patient prognosis. We also summarize the main characteristics of the genetically engineered mouse models driven by <em>MYC</em>. Finally, we assess the therapeutic potential of <em>MYC</em> inhibition in MM and the strategies currently approved for clinic use.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"66 ","pages":"Article 101177"},"PeriodicalIF":4.8,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SCFβ-TrCP targets Ajuba for degradation in a GSK3β-dependent manner in colorectal cancer","authors":"Liangshan Li ,&nbsp;Feng Zhu ,&nbsp;Yupei Liang ,&nbsp;Yuanyuan Chen ,&nbsp;Yongfu Pan ,&nbsp;Lijun Jia ,&nbsp;Shiwen Wang ,&nbsp;Hu Zhao","doi":"10.1016/j.neo.2025.101175","DOIUrl":"10.1016/j.neo.2025.101175","url":null,"abstract":"<div><div>Ajuba (ajuba LIM protein, JUB) is a member of the Ajuba family, and its oncogenic biological functions in colorectal cancer (CRC) have been extensively reported including proliferation, metastasis and resistance to chemotherapy. Although considerable studies have reported the regulation of Ajuba at the transcriptional level, the potential mechanisms of regulating Ajuba protein stability have not been fully elucidated to date. Herein, we showed that the mRNA and protein expression of Ajuba is upregulated in CRC tissues, high protein level correlates with unfavorable prognosis. Importantly, we identified Ajuba as a novel substrate of GSK3β kinase and SCF^β-TrCP E3 ubiquitin ligase. Mechanistically, GSK3β phosphorylates Ajuba at serine 163 in the highly conserved degron motif (TS¹⁶³GIS), which determines the interaction between Ajuba and the C-terminal WD40 domain of β-TrCP, and subsequent ubiquitination and targeted proteasomal degradation of Ajuba by β-TrCP. Conversely, the S163A mutant significantly attenuates the ubiquitination level of Ajuba. Overall, our study reveals a novel regulatory mechanism of Ajuba at post-translational level and sheds light on the role of GSK3β-β-TrCP axis in the turnover of Ajuba in CRC.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"66 ","pages":"Article 101175"},"PeriodicalIF":4.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response of GEM models of neuroblastoma to cabozantinib assessed by multiparametric magnetic resonance imaging","authors":"Gilberto S. Almeida ,&nbsp;Philippa King ,&nbsp;Albert Hallsworth ,&nbsp;Hannah Webber ,&nbsp;Sergey Popov ,&nbsp;Susana Miranda ,&nbsp;Orli Yogev ,&nbsp;Andrew D.J. Pearson ,&nbsp;Louis Chesler ,&nbsp;Yann Jamin ,&nbsp;Simon P. Robinson","doi":"10.1016/j.neo.2025.101170","DOIUrl":"10.1016/j.neo.2025.101170","url":null,"abstract":"<div><h3>Background</h3><div>In neuroblastoma <em>MYCN</em> amplification is associated with enhanced angiogenesis and poor survival. Mutations in the anaplastic lymphoma kinase (<em>ALK</em>) gene can occur with <em>MYCN</em> amplification, conferring a very poor prognosis. Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF)/c-MET signalling are implicated in neuroblastoma progression. Cabozantinib has potent activity against VEGFR2 and MET.</div></div><div><h3>Methods</h3><div>The efficacy of cabozantinib against tumours arising in GEM models of high-risk neuroblastoma was assessed using multiparametric MRI. Tumour-bearing Th-<em>MYCN</em> and Th-<em>ALK^F1174L</em>/Th-<em>MYCN</em> mice were imaged prior to, 24 and 48 hrs after treatment with either 30mg/kg/day cabozantinib or vehicle. Treatment-induced changes in tumour volume, native T₁, R₂* and ADC were evaluated, and histological correlates sought. Additional Th-<em>MYCN</em> mice were treated daily for up to 28 days.</div></div><div><h3>Results</h3><div>Cabozantinib elicited significant 24 and 60 % growth delay 24 and 48 hrs after treatment in tumours in Th-<em>MYCN</em> mice, and a significant 6-8 % reduction in native T₁. Tumour R₂* was significantly reduced 48 hrs post-treatment. Significantly higher tumour necrosis and apoptosis, and significantly lower Ki67, CD34 and VEGFR2 staining, was determined from the cabozantinib-treated mice. Treatment of Th-<em>ALK^F1174L</em>/Th-<em>MYCN</em> mice caused significant 4 % and 21 % tumour growth delay, and a significant 5 % reduction in native T₁ at 48 hrs. Daily cabozantinib treatment of Th-<em>MYCN</em> mice elicited significant tumour growth delay over 7 days which translated into significant survival benefit.</div></div><div><h3>Conclusion</h3><div>Cabozantinib exhibits activity against neuroblastomas arising in both Th-<em>MYCN</em> and Th-<em>MYCN</em>/<em>ALK^F1174L</em> mice, revealed <em>in situ</em> using MRI. Native T₁ is an early, sensitive and clinically translatable imaging biomarker of effective treatment response in neuroblastoma.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"65 ","pages":"Article 101170"},"PeriodicalIF":4.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High metastatic tumor-derived CXCL16 mediates liver colonization metastasis by inducing Kupffer cell polarization via the PI3K/AKT/FOXO3a pathway","authors":"Yin Liu ,&nbsp;Yunpeng Zhai ,&nbsp;Yi Zhang ,&nbsp;Liming Song ,&nbsp;Hanyue Zhang ,&nbsp;Jiahui Cao ,&nbsp;Senfeng Zhao ,&nbsp;Yahui Wu ,&nbsp;Ruopeng Liang ,&nbsp;Rongtao Zhu ,&nbsp;Weijie Wang ,&nbsp;Yuling Sun","doi":"10.1016/j.neo.2025.101174","DOIUrl":"10.1016/j.neo.2025.101174","url":null,"abstract":"<div><div>Liver metastases represent a late-stage manifestation of numerous cancers, often associated with poor patient prognosis. Kupffer cells (KCs), resident liver macrophages, play a critical role in liver metastasis (LM). However, the mechanisms by which the polarization of KCs facilitate colorectal cancer (CRC) liver metastases remain elusive. Here, we established a CRC liver metastasis mouse model and employed a co-culture system, found that KCs were recruited and polarized to M2 phenotype. We isolated and purified highly metastatic cell lines to reveal potential changes in CRC cells during metastasis. Through bulk RNA sequencing, we identified and validated CXCL16 as a positive mediator in liver-metastatic CT26-LM cells that induced an M2-like KC phenotype. Knock down of CXCL16 reduced the M2 polarization of KCs and inhibited the formation of liver metastasis lesions. Next, this polarization process was shown to be achieved through the PI3K/AKT/FOXO3a pathway. Further investigation revealed FOXO3a transcriptionally activates CD206(MRC1) in this process. Pharmacological inhibition of the CXCL16-PI3K-FOXO3a axis to disrupt the polarization of KCs attenuated CRC liver metastasis in vivo. Our findings collectively indicate that targeting the CXCL16/PI3K/AKT/FOXO3a pathway in KCs may represent a promising therapeutic strategy for preventing CRC liver metastasis.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"65 ","pages":"Article 101174"},"PeriodicalIF":4.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Antitumor Action of a Novel Histone Deacetylase Inhibitor, YF479, in Breast Cancer” [Neoplasia. 2014 Aug;16(8):665-77]","authors":"Tao Zhang ,&nbsp;Yihua Chen ,&nbsp;Jingjie Li ,&nbsp;Feifei Yang ,&nbsp;Haigang Wu ,&nbsp;Fujun Dai ,&nbsp;Meichun Hu ,&nbsp;Xiaoling Lu ,&nbsp;Yi Peng ,&nbsp;Mingyao Liu ,&nbsp;Yongxiang Zhao ,&nbsp;Zhengfang Yi","doi":"10.1016/j.neo.2025.101168","DOIUrl":"10.1016/j.neo.2025.101168","url":null,"abstract":"","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"65 ","pages":"Article 101168"},"PeriodicalIF":4.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of patient-derived 3D in vitro models of sarcomas: literature review and guidelines on behalf of the FORTRESS working group","authors":"Lore De Cock ,&nbsp;Ieva Palubeckaitė ,&nbsp;Francesca Bersani ,&nbsp;Tobias Faehling ,&nbsp;Sandro Pasquali ,&nbsp;Sam Umbaugh ,&nbsp;Michael Torsten Meister ,&nbsp;Molly R. Danks ,&nbsp;Piotr Manasterski ,&nbsp;Richard Miallot ,&nbsp;Manuela Krumbholz ,&nbsp;Siyer Roohani ,&nbsp;Dominique Heymann ,&nbsp;Florencia Cidre-Aranaz ,&nbsp;Agnieszka Wozniak ,&nbsp;Patrick Schöffski ,&nbsp;Judith V.M.G. Bovée ,&nbsp;Alessandra Merlini ,&nbsp;Sanne Venneker","doi":"10.1016/j.neo.2025.101171","DOIUrl":"10.1016/j.neo.2025.101171","url":null,"abstract":"<div><div>Sarcomas are a large family of rare and heterogeneous mesenchymal tumors, which respond poorly to available systemic treatments. Translation of preclinical findings into clinical applications has been slow, limiting improvements in patients’ outcomes and ultimately highlighting the need for a better understanding of sarcoma biology to develop more effective, subtype-specific therapies. To this end, reliable preclinical models are crucial, but the development of 3D <em>in vitro</em> sarcoma models has been lagging behind that of epithelial cancers. This is primarily due to the rarity and heterogeneity of sarcomas, and lack of widespread knowledge regarding the optimal growth conditions of these <em>in vitro</em> models. In this review, we provide an overview of currently available sarcoma tumoroid models, together with guidelines and suggestions for model development and characterization, on behalf of the FORTRESS (Forum For Translational Research in Sarcomas) international research working group on 3D sarcoma models.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"65 ","pages":"Article 101171"},"PeriodicalIF":4.8,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA-methylation eraser TET2 activates WTIP expression to suppress an AKT-dependent chemoresistance of gastric cancer","authors":"Yan Guo ,&nbsp;Hongyang Yu ,&nbsp;Jinyang Li ,&nbsp;Kewei Liu ,&nbsp;Mengyi Han ,&nbsp;Yuxin Tang ,&nbsp;Li Su ,&nbsp;Xianfeng Li ,&nbsp;Haixia Wu ,&nbsp;Dongfeng Chen","doi":"10.1016/j.neo.2025.101166","DOIUrl":"10.1016/j.neo.2025.101166","url":null,"abstract":"<div><div>Chemoresistance is one of the major causes of the failure in gastric cancer (GC) treatment and leads to poor clinical outcomes. Ten-eleven translocation (TET) 2 expression and activity are frequently reduced in solid tumors. However, whether TET2 participants in GC chemoresistance remains poorly understood. In this study, we demonstrated that the TET2 acts as a novel suppressor of GC chemoresistance. TET2 and transcription factor PATZ1 work together to promote the expression of WTIP. WTIP interacts with PP2A to inhibit the T308 phosphorylation and kinase activity of AKT, thereby suppressing stemness and chemoresistance of GC. Thus, the novel TET2-WTIP transcriptional axis, which is frequently silenced, suppresses an AKT-dependent chemoresistance of GC. TET2, combined with WTIP and AKT-pT308, can synergistically serve as a biomarker for predicting chemotherapy response in GC patients. Furthermore, we highlight that combining AKT inhibitor with chemotherapy is a promising therapeutic strategy for TET2-silenced GCs with chemoresistance in clinic.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"65 ","pages":"Article 101166"},"PeriodicalIF":4.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “PRMT1 methylates METTL14 to modulate its oncogenic function” [Neoplasia 42 (2023) 100912]","authors":"Jingchao Wang ,&nbsp;Zhen Wang ,&nbsp;Hiroyuki Izunuka ,&nbsp;Wenyi Wei ,&nbsp;Jing Liu","doi":"10.1016/j.neo.2025.101167","DOIUrl":"10.1016/j.neo.2025.101167","url":null,"abstract":"","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"65 ","pages":"Article 101167"},"PeriodicalIF":4.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An antibody targeting an immune checkpoint molecule BTN2A2 enhances anti-tumor immunity","authors":"Li Xiao ,&nbsp;Rong Hu ,&nbsp;Wei Chen ,&nbsp;Jie Gao ,&nbsp;Youbo Zhao ,&nbsp;Zuli Wang ,&nbsp;Guangshi Du ,&nbsp;Yishen Tian ,&nbsp;Laijun Lai ,&nbsp;Lu Liu ,&nbsp;Min Su","doi":"10.1016/j.neo.2025.101161","DOIUrl":"10.1016/j.neo.2025.101161","url":null,"abstract":"<div><div>Tumors exploit immune checkpoints to evade immune responses. Therefore, targeting these checkpoints has become a key strategy in cancer immunotherapy. In this study, we have developed a novel immune checkpoint inhibitor (ICI) targeting the B7 family-related molecule BTN2A2. The human BTN2A2 protein, which was highly expressed in some tumor tissues and activated antigen-presenting cells (APCs), can inhibit T cell activation and proliferation. The anti-BTN2A2 monoclonal antibody (mAb) can neutralize the inhibitory effect of BTN2A2 on T cells. In mouse models of pancreatic cancer and glioma, compared to the control group, the anti-BTN2A2 treatment group exhibited tumor shrinkage of 35.8 % (<em>P</em> &lt; 0.05) and 51.2 % (<em>P</em> &lt; 0.01), respectively, along with increased CD8+ tumor-infiltrating lymphocytes (TILs) by 1.7-fold (<em>P</em> &lt; 0.001) and 2.2-fold (<em>P</em> &lt; 0.001), respectively. In addition, anti-BTN2A2 mAb also increased the infiltration of B cells, M1 macrophages, and the expression of inflammatory cytokines in T cells, while reducing the infiltration of M2 macrophages, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs). Thus, anti-hBTN2A2 mAb normalizes the immunodeficient tumor microenvironment (TME) and inhibits tumor growth. Our results suggest that targeting the BTN2A2 immune checkpoint may represent a novel strategy for cancer treatment, especially in immunosuppressive 'cold' tumors.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"65 ","pages":"Article 101161"},"PeriodicalIF":4.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of PERK/eIF2α/ATF4 signaling inhibits ERα expression in breast cancer","authors":"Yuanli Wu ,&nbsp;Gang Wang ,&nbsp;Ruixue Yang ,&nbsp;Duanfang Zhou ,&nbsp;Qingjuan Chen ,&nbsp;Qiuya Wu ,&nbsp;Bo Chen ,&nbsp;Lie Yuan ,&nbsp;Na Qu ,&nbsp;Hongmei Wang ,&nbsp;Moustapha Hassan ,&nbsp;Ying Zhao ,&nbsp;Mingpu Liu ,&nbsp;Zhengze Shen ,&nbsp;Weiying Zhou","doi":"10.1016/j.neo.2025.101165","DOIUrl":"10.1016/j.neo.2025.101165","url":null,"abstract":"<div><div>Approximately 70–80% of breast cancers rely on estrogen receptor alpha (ERα) for growth. The unfolded protein response (UPR), a cellular response to endoplasmic reticulum stress (ERS), is an important process crucial for oncogenic transformation. The effect of ERS on ERα expression and signaling remains incompletely elucidated. Here, we focused on the regulatory mechanisms of ERS on ERα expression in ER-positive breast cancer (ER+ BC). Our results demonstrate that ERα protein and mRNA levels in ER+ BC cells are considerably reduced by the ERS inducers thapsigargin (TG) and brefeldin A (BFA) via the PERK/eIF2α/ATF4 signaling pathway. ChIP-qPCR and luciferase reporter gene analysis revealed that ERS induction facilitated ATF4 binding to the <em>ESR1</em> (the gene encoding ERα) promoter region, thereby suppressing <em>ESR1</em> promoter activity and inhibiting ERα expression. Furthermore, selective activation of PERK signaling or ATF4 overexpression attenuated ERα expression and tumor cell growth both <em>in vitro</em> and <em>in vivo</em>. In conclusion, our results demonstrate that ERS suppresses ERα expression transcriptionally via the PERK/eIF2α/ATF4 signaling. Our study provides insights into the treatment of ER+ BC by targeting ERα signaling through selective activation of the PERK branch of the UPR.</div></div>","PeriodicalId":18917,"journal":{"name":"Neoplasia","volume":"65 ","pages":"Article 101165"},"PeriodicalIF":4.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}