Molecular Oncology最新文献_第7页

Correction to "Differential activity of MEK and ERK inhibitors in BRAF inhibitor resistant melanoma". 更正“MEK和ERK抑制剂在BRAF抑制剂耐药黑色素瘤中的差异活性”。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-08-01 Epub Date: 2026-07-12 DOI: 10.1002/1878-0261.70297

引用次数: 0

EXPRESSION OF CONCERN: A Newly Identified 45-kDa JAK2 Variant with an Altered Kinase Domain Structure Represents a Novel Mode of JAK2 Kinase Inhibitor Resistance. 关注表达：一种新发现的45-kDa JAK2突变体，其激酶结构域结构改变代表了JAK2激酶抑制剂耐药的一种新模式。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-08-01 Epub Date: 2026-06-21 DOI: 10.1002/1878-0261.70294

引用次数: 0

Heterozygous loss-of-function alleles associate the conserved 3'-5' exoribonuclease EXOSC10 with hypersensitivity to the anticancer drug 5-fluorouracil. 杂合子功能缺失等位基因将保守的3‘-5’外核糖核酸酶EXOSC10与对抗癌药物5-氟尿嘧啶的超敏反应联系起来。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-08-01 Epub Date: 2026-05-15 DOI: 10.1002/1878-0261.70239

Radhika Sain, Yann Le Page, Frédéric Percevault, Emmanuelle Becker, Luc Negroni, Almudena Fernandez, Marta Cantero, Diego Muñoz-Santos, Lluís Montoliu, Cyrille Garnier, Michael Primig

{"title":"Heterozygous loss-of-function alleles associate the conserved 3'-5' exoribonuclease EXOSC10 with hypersensitivity to the anticancer drug 5-fluorouracil.","authors":"Radhika Sain, Yann Le Page, Frédéric Percevault, Emmanuelle Becker, Luc Negroni, Almudena Fernandez, Marta Cantero, Diego Muñoz-Santos, Lluís Montoliu, Cyrille Garnier, Michael Primig","doi":"10.1002/1878-0261.70239","DOIUrl":"10.1002/1878-0261.70239","url":null,"abstract":"The 3'-5' exoribonuclease EXOSC10 degrades aberrant mRNAs and noncoding RNAs in cooperation with the nuclear RNA exosome. EXOSC10's localization and stability are regulated by sumoylation and proteasomal degradation in response to stress, and the protein is essential for cell growth and proliferation, fertility, hematopoiesis, and brain development. EXOSC10 is a cancer biomarker; its activity is inhibited by the widely used anticancer drug 5-fluorouracil (5-FU) and the protein's depletion sensitizes cells to 5-FU. We employed mass spectrometry to reveal EXOSC10's post-translational modifications, such as phosphorylation, acetylation and ubiquitination, and to explore its protein interaction network, which includes RNA exosome subunits and enzymes involved in protein degradation. Furthermore, we find that the EXOSC10S402T allele identified in colon cancer and located within a motif for targeted proteolysis is stable, nuclear but nonfunctional in vivo, since homozygous Exosc10S402T mice exhibit early embryonic lethality. We identified equivalent S402P/S402A variants and heterozygous loss-of-function (LoF) alleles in cancers and healthy individuals using public genomics data. Our findings suggest that recessive EXOSC10 LoF alleles may cause increased 5-FU sensitivity in tumors bearing de novo mutations and hypertoxicity in heterozygous carriers.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1913-1932"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

RETRACTION: Novel C-Terminal Heat Shock Protein 90 Inhibitors Target Breast Cancer Stem Cells and Block Migration, Self-Renewal, and Epithelial-Mesenchymal Transition. 缩回：新型c端热休克蛋白90抑制剂靶向乳腺癌干细胞并阻断迁移、自我更新和上皮-间质转化。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-08-01 Epub Date: 2026-07-09 DOI: 10.1002/1878-0261.70300

{"title":"RETRACTION: Novel C-Terminal Heat Shock Protein 90 Inhibitors Target Breast Cancer Stem Cells and Block Migration, Self-Renewal, and Epithelial-Mesenchymal Transition.","authors":"","doi":"10.1002/1878-0261.70300","DOIUrl":"10.1002/1878-0261.70300","url":null,"abstract":"Retraction: C. Subramanian, P. T. Grogan, T. Wang, J. Bazzill, A. Zuo, P. T. White, A. Kalidindi, D. Kuszynski, G. Wang, B. S. J. Blagg and M. S. Cohen, \"Novel C-Terminal Heat Shock Protein 90 Inhibitors Target Breast Cancer Stem Cells and Block Migration, Self-Renewal, and Epithelial-Mesenchymal Transition,\" Molecular Oncology 14, no. 9 (2020): 2058-2068, https://doi.org/10.1002/1878-0261.12686. The above article, published online on 07 April 2020 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Kevin Ryan; FEBS Press; and John Wiley & Sons Ltd. The retraction has been agreed following concerns raised by a third party. An investigation identified that the control, KU711 and 17-AAG liver and kidney panels shown in Figure 6B were duplicated from another article published earlier by some of the same authors. The reused images were presented to represent a different cell line. The authors cooperated with the investigation and explained that this was an inadvertent error; they also provided some supporting data. However, the data provided was not sufficient to restore the editors' confidence in the article's results and conclusions. Therefore, the editors consider the results and conclusions to be unreliable. The authors disagree with the retraction.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2132"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

CD47 promotes mitogen-activated protein kinase and epithelial-to-mesenchymal transition molecular programs to drive prometastatic phenotypes in non-small cell lung cancer. 在非小细胞肺癌中，CD47促进丝裂原活化蛋白激酶和上皮到间质转化分子程序驱动前转移表型。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-08-01 Epub Date: 2026-04-20 DOI: 10.1002/1878-0261.70237

Asa P Y Lau, Lilian G Zhai, Ryunosuke Hoshi, Zackary Rousseau, Abraam Zakhary, Yin Fang Wu, Rola M Saleeb, Heyu Ni, Kelsie L Thu

{"title":"CD47 promotes mitogen-activated protein kinase and epithelial-to-mesenchymal transition molecular programs to drive prometastatic phenotypes in non-small cell lung cancer.","authors":"Asa P Y Lau, Lilian G Zhai, Ryunosuke Hoshi, Zackary Rousseau, Abraam Zakhary, Yin Fang Wu, Rola M Saleeb, Heyu Ni, Kelsie L Thu","doi":"10.1002/1878-0261.70237","DOIUrl":"10.1002/1878-0261.70237","url":null,"abstract":"CD47 is best known for its role in tumor immune evasion; however, studies in diverse cell models indicate that it also has cell autonomous, tumor-promoting functions which are cell type- and context-specific. Motivated by the prognostic and therapeutic significance of CD47 and the limited knowledge regarding its roles beyond immune evasion in non-small cell lung cancer (NSCLC), we sought to define the cellular and molecular processes driven by intrinsic CD47 signaling in NSCLC. Transcriptome profiling of CD47 wild-type and knockout NSCLC cells implicated its regulation of genes enriched for signatures of mitogen-activated protein kinase (MAPK) signaling and epithelial-to-mesenchymal transition (EMT). A significant positive association between CD47 and MAPK/EMT expression signatures was also evident in large cohorts of NSCLC cell lines and tumor tissues. Functional studies indicated that CD47 does not regulate cell proliferation in NSCLC cells like it does in other cancer types. Instead, CD47 regulates cell adhesion and migration through an ERK and EMT axis, validating our transcriptomic findings. Moreover, CD47 loss-of-function significantly diminished the ability of NSCLC cells to metastasize in vivo, demonstrating the physiological relevance of cell-intrinsic CD47 signaling in lung cancer cells. Our data reveal a novel role for CD47 in relaying signals through ERK to promote EMT expression programs and prometastatic phenotypes in NSCLC. Although additional mechanistic studies are needed to further decipher the CD47-ERK-EMT signaling pathway, our findings reinforce the therapeutic potential of CD47, rationalizing further research to develop CD47 blockade as a multimodal therapy for NSCLC.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1963-1985"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13399593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Interpreting the effects of DNA polymerase variants at the structural level. 在结构水平上解释DNA聚合酶变异的影响。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-08-01 Epub Date: 2026-05-27 DOI: 10.1002/1878-0261.70255

Matteo Arnaudi, Karolina Krzesińska, Ludovica Beltrame, Pablo Sánchez-Izquierdo Besora, Matteo Tiberti, Mef Nilbert, Anna Rohlin, Elena Papaleo

{"title":"Interpreting the effects of DNA polymerase variants at the structural level.","authors":"Matteo Arnaudi, Karolina Krzesińska, Ludovica Beltrame, Pablo Sánchez-Izquierdo Besora, Matteo Tiberti, Mef Nilbert, Anna Rohlin, Elena Papaleo","doi":"10.1002/1878-0261.70255","DOIUrl":"10.1002/1878-0261.70255","url":null,"abstract":"Genetic variants in the DNA polymerase enzymes POLE and POLD1 can affect protein function by altering stability, catalysis, DNA binding, and interactions with other biomolecules. Understanding the structural basis of these variants is important for a comprehensive interpretation of variant impact. In this study, we used MAVISp, a modular structure-based framework, and molecular dynamics simulations to analyze over 60 000 missense variants of POLE and POLD1. By integrating results from changes in folding and binding free energies, local alterations in the proximity of the active or phosphorylation sites, we provided a detailed structural interpretation of variants reported across various databases, including ClinVar, COSMIC, and cBioPortal. Moreover, we predicted the functional consequences of variants not found yet in disease-related databases, thereby creating a comprehensive catalog for future studies. Of note, our approach enabled us to classify 364 Variants of Uncertain Significance (VUS) as PP3 evidence and 323 as BP4 evidence, in accordance with the American College of Medical Genetics and Genomics (ACMG) guidelines. Additionally, we identified a group of variants that could alter the native orientation of the residues within the catalytic site of the exonuclease domain, such as POLE variants P297S and P436R. Finally, we identified a group of variants predicted to affect DNA-binding affinity and rationalized their effects in terms of different energetic contributions and structural features. Collectively, our results not only advance our understanding of protein variant effects in POLE and POLD1 at the structural level but also support future studies aimed at variant classification, variant prioritization for experimental studies, and functional interpretation across diverse biological contexts.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2054-2084"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148042836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Astrocyte heterogeneity in brain metastases. 脑转移中的星形胶质细胞异质性。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-08-01 Epub Date: 2026-07-08 DOI: 10.1002/1878-0261.70296

Carolina Hernández-Oliver, Neibla Priego, Manuel Valiente

{"title":"Astrocyte heterogeneity in brain metastases.","authors":"Carolina Hernández-Oliver, Neibla Priego, Manuel Valiente","doi":"10.1002/1878-0261.70296","DOIUrl":"10.1002/1878-0261.70296","url":null,"abstract":"Brain metastasis is increasingly understood as a disease of reciprocal adaptation between metastatic cells and the brain microenvironment. Among host cells, astrocytes have emerged as central regulators of metastatic colonization, survival, immune remodeling, and treatment resistance. Recent studies are re-defining astrocytes to explore the functional implications of their cellular heterogeneity. Evidence in brain metastasis indicates that astrocyte responses are heterogeneous across anatomical space, stage of colonization, and tumor type. This framework helps explaining how distinct astrocyte programs can coexist and why no single experimental platform captures their organization and complex biology. Moving toward spatially resolved, longitudinal, and functionally validated definitions of astrocyte states could clarify mechanisms and guide more precise therapeutic opportunities in brain metastasis. In this Viewpoint, we examine studies that have challenged the long-standing paradigm of astrocytes as a uniform entity, highlighting how recent technological advances reinforce previous findings and pave the way for identifying new therapeutic targets.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1895-1904"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13399075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

From tumor-centric to ecosystem-based hypotheses in brain tumor research and care: Proceedings from The second Brain Tumor Meeting by the Sea organized by Julie Gavard and Eric Chevet, held in St Malo (France), 23-25 March 2026. 从肿瘤中心到基于生态系统的脑肿瘤研究和护理假说：Julie Gavard和Eric Chevet于2026年3月23日至25日在法国圣马洛举办的第二届海上脑肿瘤会议记录。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-08-01 Epub Date: 2026-07-04 DOI: 10.1002/1878-0261.70298

Julie Gavard, Flavie Bénard, Eva Billat, Margaux Le Guyon, Victoria Maltret, Laura Merlet, Chloé Astrid Walter, Tony Avril, Eric Chevet

{"title":"From tumor-centric to ecosystem-based hypotheses in brain tumor research and care: Proceedings from The second Brain Tumor Meeting by the Sea organized by Julie Gavard and Eric Chevet, held in St Malo (France), 23-25 March 2026.","authors":"Julie Gavard, Flavie Bénard, Eva Billat, Margaux Le Guyon, Victoria Maltret, Laura Merlet, Chloé Astrid Walter, Tony Avril, Eric Chevet","doi":"10.1002/1878-0261.70298","DOIUrl":"10.1002/1878-0261.70298","url":null,"abstract":"Brain tumors remain among the most lethal cancers, largely due to their remarkable heterogeneity, plasticity, and resistance to therapy. The second Brain Tumor Meeting by the Sea (Saint-Malo, France, 2026) brought together researchers, clinicians, and patient representatives to discuss emerging concepts shaping the future of neuro-oncology. A recurring theme was the shift from a tumor-centric perspective toward an ecosystem-based view that integrates tumor cells, microenvironmental cues, developmental context, and patient-centered dimensions. Advances in patient-derived models, multi-omics approaches, spatial technologies, and artificial intelligence are refining tumor classification and revealing novel therapeutic vulnerabilities. Discussions highlighted cellular plasticity and stress-adaptation mechanisms as key drivers of tumor evolution and treatment resistance. They also emphasized the need for identifying dynamic biomarkers and developing more physiologically relevant disease models. Beyond biological discoveries, the meeting underscored the importance of strengthening interactions among research, clinical care, and patient communities. Together, these advances support a more integrated framework for understanding brain tumors and developing future therapeutic strategies.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1905-1912"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Special Issue: EACR 2026 Congress: Innovative Cancer Science, 8-11 June 2026. 特刊：EACR 2026大会：创新癌症科学，2026年6月8-11日。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-08-01 DOI: 10.1002/1878-0261.70318

引用次数: 0

Proteasome inhibitor, ixazomib prevents topoisomerase-I degradation and reverses irinotecan resistance in colorectal cancer. 蛋白酶体抑制剂ixazomib可阻止拓扑异构酶i降解并逆转结直肠癌患者对伊立替康的耐药性。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-08-01 Epub Date: 2026-04-15 DOI: 10.1002/1878-0261.70256

Yuho Ebata, Koji Ando, Hirofumi Hasuda, Koshi Mimori, Elizabeth C Unan, Siddhartha Pulukuri, Aahana Tiku, Allison Berger, Eiji Oki, Ajit Bharti, Tomoharu Yoshizumi

{"title":"Proteasome inhibitor, ixazomib prevents topoisomerase-I degradation and reverses irinotecan resistance in colorectal cancer.","authors":"Yuho Ebata, Koji Ando, Hirofumi Hasuda, Koshi Mimori, Elizabeth C Unan, Siddhartha Pulukuri, Aahana Tiku, Allison Berger, Eiji Oki, Ajit Bharti, Tomoharu Yoshizumi","doi":"10.1002/1878-0261.70256","DOIUrl":"10.1002/1878-0261.70256","url":null,"abstract":"Irinotecan, a topoisomerase I (topoI) inhibitor, is widely used for colorectal cancer, but resistance remains a major clinical challenge. We previously showed that camptothecin induces ubiquitin-proteasome pathway (UPP)-mediated topoI degradation. In this study, we investigated whether inhibition of UPP could prevent topoI degradation and restore camptothecin sensitivity. SN-38, an active metabolite of irinotecan, induced topoI degradation in irinotecan-resistant colorectal cancer cell lines, which was suppressed by ixazomib. The combination significantly enhanced cytotoxicity, colony inhibition, and reduced IC50 values compared with SN-38 alone. Mechanistically, ixazomib prevented proteasome-mediated degradation of ubiquitinated topoI, restoring its stability. In vivo, the combination significantly suppressed tumor growth in a DLD-1 xenograft model compared with SN-38 alone. These findings indicate that UPP-dependent topoI degradation is a key mechanism underlying irinotecan resistance in colorectal cancer. Pharmacological inhibition of the proteasome effectively prevents topoI loss and restores irinotecan sensitivity, suggesting that proteasome inhibitors such as ixazomib may serve as promising therapeutic partners for camptothecin-based chemotherapy.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2114-2128"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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