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Multimodal sequencing of neoadjuvant nivolumab treatment in hepatocellular carcinoma reveals cellular and molecular immune landscape for drug response
IF 37.3 1区 医学
Molecular Cancer Pub Date : 2025-04-09 DOI: 10.1186/s12943-025-02314-w
Fanhong Zeng, Qingyang Zhang, Yu-Man Tsui, Huanhuan Ma, Lu Tian, Abdullah Husain, Jingyi Lu, Joyce Man-Fong Lee, Vanilla Xin Zhang, Po-Man Li, Gary Cheuk-Hang Cheung, Tan-To Cheung, Daniel Wai-Hung Ho, Irene Oi-Lin Ng
{"title":"Multimodal sequencing of neoadjuvant nivolumab treatment in hepatocellular carcinoma reveals cellular and molecular immune landscape for drug response","authors":"Fanhong Zeng, Qingyang Zhang, Yu-Man Tsui, Huanhuan Ma, Lu Tian, Abdullah Husain, Jingyi Lu, Joyce Man-Fong Lee, Vanilla Xin Zhang, Po-Man Li, Gary Cheuk-Hang Cheung, Tan-To Cheung, Daniel Wai-Hung Ho, Irene Oi-Lin Ng","doi":"10.1186/s12943-025-02314-w","DOIUrl":"https://doi.org/10.1186/s12943-025-02314-w","url":null,"abstract":"A striking characteristic of liver cancer is its extensive heterogeneity, particularly with regard to its varied response to immunotherapy. In this study, we employed multimodal sequencing approaches to explore the various aspects of neoadjuvant nivolumab treatment in liver cancer patients. We used spatially-resolved transcriptomics, single- and bulk-cell transcriptomics, and TCR clonotype analyses to examine the spatiotemporal dynamics of the effects of nivolumab. We observed a significantly higher clonal expansion of T cells in the tumors of patients who responded to the treatment, while lipid accumulation was detected in those of non-responders, likely due to inherent differences in lipid metabolic processes. Furthermore, we found a preferential enrichment of T cells, which was associated with a better drug response. Our results also indicate a functional antagonism between tumor-associated macrophages (TAMs) and CD8 cells and their spatial separation. Notably, we identified a UBASH3B/NR1I2/CEACAM1/HAVCR2 signaling axis, highlighting the intense communication among TAMs, tumor cells, and T-cells that leads to pro-tumorigenic outcomes resulting in poorer nivolumab response. In summary, using integrative multimodal sequencing investigations, combined with the multi-faceted exploration of pre- and post-treatment samples of neoadjuvant nivolumab-treated HCC patients, we identified useful mechanistic determinants of therapeutic response. We also reconstructed the spatiotemporal model that recapitulates the physiological restoration of T cell cytotoxicity by anti-PD1 blockade. Our findings could provide important biomarkers and explain the mechanistic basis differentiating the responders and non-responders.\u0000","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"21 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805933","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
Single-cell and spatial transcriptomic analyses revealing tumor microenvironment remodeling after neoadjuvant chemoimmunotherapy in non-small cell lung cancer
IF 37.3 1区 医学
Molecular Cancer Pub Date : 2025-04-09 DOI: 10.1186/s12943-025-02287-w
Xiaolu Cui, Siyuan Liu, He Song, Jingjing Xu, Yanbin Sun
{"title":"Single-cell and spatial transcriptomic analyses revealing tumor microenvironment remodeling after neoadjuvant chemoimmunotherapy in non-small cell lung cancer","authors":"Xiaolu Cui, Siyuan Liu, He Song, Jingjing Xu, Yanbin Sun","doi":"10.1186/s12943-025-02287-w","DOIUrl":"https://doi.org/10.1186/s12943-025-02287-w","url":null,"abstract":"Non-small cell lung cancer (NSCLC) represents the most common pathological type of lung cancer, and the combination of neoadjuvant immunotherapy with chemotherapy has emerged as the first-line treatment for NSCLC. Nevertheless, the efficacy of this therapeutic approach remains variable. The present study aims to examine the impact of chemoimmunotherapy in NSCLC patients, with a view to identifying key molecules, critical cell subpopulations, communication patterns and spatial distributions that potentially correlate with therapeutic sensitivity. A total of 16 lung cancer tissue samples were collected from a cohort of 12 NSCLC patients and subjected to single-cell RNA and spatial transcriptome sequencing. Our data demonstrated that the distribution of CD4 + Treg T cells and mCAFs indicated an immunosuppressive tumor microenvironment, while the accumulation of CD4 + Th17 T cells and iCAFs could act as a positive marker for the sensitivity to chemoimmunotherapy. Furthermore, a significant high level of SELENOP-macrophages was observed in tissues from positive responders, and a strong co-localization between SELENOP-macrophages and antigen-presenting cancer associated fibroblasts (CAFs) in the tumor boundaries was identified, indicating the cooperative roles of these two cell types in response to combined therapy. Moreover, SELENOP-macrophages were observed to be accumulated in tertiary lymphoid structures, which further suggested its critical role in recruiting lymphocytes. Furthermore, analysis of cell–cell communication, based on spatial transcriptomics, suggests that the interactions between SELENOP-macrophages, apCAFs, CD4 + and CD8 + T cells were significantly enhanced in responders. In addition, SELENOP-macrophages recruited CD4 + Naïve, Helper and CD8 + Naïve T cells through pathways such as the cholesterol, interleukin, chemokine and HLA when responding to combined therapy. The present study further unveils the dynamic spatial and transcriptional changes in the tumor microenvironment of non-small cell lung cancer in response to combination therapy. ","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"31 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805932","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
Caveolin-1: an ambiguous entity in breast cancer
IF 37.3 1区 医学
Molecular Cancer Pub Date : 2025-04-07 DOI: 10.1186/s12943-025-02297-8
Naveen Chintalaramulu, Dhirendra Pratap Singh, Biplov Sapkota, Dayanidhi Raman, Suresh Alahari, Joseph Francis
{"title":"Caveolin-1: an ambiguous entity in breast cancer","authors":"Naveen Chintalaramulu, Dhirendra Pratap Singh, Biplov Sapkota, Dayanidhi Raman, Suresh Alahari, Joseph Francis","doi":"10.1186/s12943-025-02297-8","DOIUrl":"https://doi.org/10.1186/s12943-025-02297-8","url":null,"abstract":"Breast cancer (BC) is the most frequently diagnosed cancer in women and the second leading cause of death from cancer among women. Metastasis is the major cause of BC-associated mortality. Accumulating evidence implicates Caveolin-1 (Cav-1), a structural protein of plasma membrane caveolae, in BC metastasis. Cav-1 exhibits a dual role, as both a tumor suppressor and promoter depending on the cellular context and BC subtype. This review highlights the role of Cav-1 in modulating glycolytic metabolism, tumor-stromal interactions, apoptosis, and senescence. Additionally, stromal Cav-1's expression is identified as a potential prognostic marker, offering insights into its contrasting roles in tumor suppression and progression. Furthermore, Cav-1's context-dependent effects are explored in BC subtypes including hormone receptor-positive, HER2-positive, and triple-negative BC (TNBC). The review further delves into the role of Cav-1 in regulating the metastatic cascade including extracellular matrix interactions, cell migration and invasion, and premetastatic niche formation. The later sections discuss the therapeutic targeting of Cav-1 by metabolic inhibitors such as betulinic acid and Cav-1 modulating compounds. While Cav-1 may be a potential biomarker and therapeutic target, its heterogeneous expression and context-specific activity necessitates further research to develop precise interventions. Future studies investigating the mechanistic role of Cav-1 in metastasis may pave the way for effective treatment of metastatic BC.\u0000","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"74 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143790149","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
Editorial Expression of Concern: Alterations in candidate genes PHF2, FANCC, PTCH1 and XPA at chromosomal 9q22.3 region: Pathological significance in early- and late-onset breast carcinoma
IF 37.3 1区 医学
Molecular Cancer Pub Date : 2025-04-05 DOI: 10.1186/s12943-024-02181-x
Satyabrata Sinha, Ratnesh K. Singh, Neyaz Alam, Anup Roy, Susanta Roychoudhury, Chinmay Kumar Panda
{"title":"Editorial Expression of Concern: Alterations in candidate genes PHF2, FANCC, PTCH1 and XPA at chromosomal 9q22.3 region: Pathological significance in early- and late-onset breast carcinoma","authors":"Satyabrata Sinha, Ratnesh K. Singh, Neyaz Alam, Anup Roy, Susanta Roychoudhury, Chinmay Kumar Panda","doi":"10.1186/s12943-024-02181-x","DOIUrl":"https://doi.org/10.1186/s12943-024-02181-x","url":null,"abstract":"<p><b>Correction: Mol Cancer 7, 84 (2008)</b></p><p><b>https://doi.org/10.1186/1476-4598-7-84</b>.</p><p> The Editor-in-Chief would like to alert the readers that concerns have been raised regarding some of the data presented in the figures. Specifically:</p><ul>\u0000<li>\u0000<p>In Fig. 1c (upper panel), the 588 T and 366 D9S104 bands appear highly similar, and the 4131 T D9S104 band appears highly similar to 3025 N PHF2 ex-18.</p>\u0000</li>\u0000<li>\u0000<p>In Fig. 3b, the two upper panels appear to have repetitive features in the gel backgrounds, and the bottom panel appears to have inconsistencies in the background.</p>\u0000</li>\u0000<li>\u0000<p>Figure 6c and f appear highly similar to Fig. 5d and a in [1], respectively.</p>\u0000</li>\u0000</ul><p> Due to the age of the article, the authors are unable to provide the underlying raw data to sufficiently address these concerns. Readers are therefore advised to interpret these results with caution.</p><p> All authors agree to this Editorial Expression of Concern.</p><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Sinha Satyabrata, Singh Ratnesh K, Nilanjana B, Nupur M, Susmita G, Neyaz A, Anup R, Susanta R, Chinmay Kumar P. Frequent alterations of LOH11CR2A, PIG8 and CHEK1 genes at chromosomal 11q24.1-24.2 region in breast carcinoma: clinical and prognostic implications. Mol Oncol. 2011;5. https://doi.org/10.1016/j.molonc.2011.06.005.</p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><h3>Authors and Affiliations</h3><ol><li><p>Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata, India</p><p>Satyabrata Sinha, Ratnesh K. Singh & Chinmay Kumar Panda</p></li><li><p>Department of Surgical Oncology, Chittaranjan National Cancer Institute, Kolkata, India</p><p>Neyaz Alam</p></li><li><p>Department of Pathology, Medical College, Kolkata, India</p><p>Anup Roy</p></li><li><p>Molecular and Human Genetics Division, Indian Institute of Chemical Biology, Kolkata, India</p><p>Susanta Roychoudhury</p></li></ol><span>Authors</span><ol><li><span>Satyabrata Sinha</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Ratnesh K. Singh</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Neyaz Alam</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Anup Roy</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Susanta Roychoudhury</span>View author publications<p><span>You can also search for this author in</span><span>Pu","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"95 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782396","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
Small open reading frame-encoded microproteins in cancer: identification, biological functions and clinical significance 癌症中的小开放阅读框编码微蛋白:识别、生物功能和临床意义
IF 37.3 1区 医学
Molecular Cancer Pub Date : 2025-04-02 DOI: 10.1186/s12943-025-02278-x
Tingting Zhang, Zhang Li, Jiao Li, Yong Peng
{"title":"Small open reading frame-encoded microproteins in cancer: identification, biological functions and clinical significance","authors":"Tingting Zhang, Zhang Li, Jiao Li, Yong Peng","doi":"10.1186/s12943-025-02278-x","DOIUrl":"https://doi.org/10.1186/s12943-025-02278-x","url":null,"abstract":"The human genome harbors approximately twenty thousand protein-coding genes, and a significant portion of life science research focuses on elucidating their functions and the underlying mechanisms. Recent studies have revealed that small open reading frame (sORF), originating from non-coding RNAs or the 5’ leader sequences of messenger RNAs, can be translated into small peptides called microproteins through cap-dependent or cap-independent mechanisms. These microproteins interact with diverse molecular partners to modulate gene expression at multiple regulatory levels, thereby playing critical roles in various biological processes. Notably, sORF-encoded microproteins exhibit aberrant expression patterns in cancer and are implicated in tumor initiation and progression, expanding our understanding of cancer biology. In this review, we introduce the translational mechanisms and identification methods of microproteins, summarize their dysregulation in cancer and their biological functions in regulating gene expression, and emphasize their roles in driving hallmark events of cancer. Furthermore, we discuss their clinical significance as diagnostic and prognostic biomarkers, as well as therapeutic targets.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"3 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757992","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
Regulation of cellular senescence in tumor progression and therapeutic targeting: mechanisms and pathways 肿瘤进展和靶向治疗中的细胞衰老调控:机制和途径
IF 37.3 1区 医学
Molecular Cancer Pub Date : 2025-04-02 DOI: 10.1186/s12943-025-02284-z
Bowei Liu, Zhigang Peng, Hao Zhang, Nan Zhang, Zaoqu Liu, Zhiwei Xia, Shaorong Huang, Peng Luo, Quan Cheng
{"title":"Regulation of cellular senescence in tumor progression and therapeutic targeting: mechanisms and pathways","authors":"Bowei Liu, Zhigang Peng, Hao Zhang, Nan Zhang, Zaoqu Liu, Zhiwei Xia, Shaorong Huang, Peng Luo, Quan Cheng","doi":"10.1186/s12943-025-02284-z","DOIUrl":"https://doi.org/10.1186/s12943-025-02284-z","url":null,"abstract":"Cellular senescence, a stable state of cell cycle arrest induced by various stressors or genomic damage, is recognized as a hallmark of cancer. It exerts a context-dependent dual role in cancer initiation and progression, functioning as a tumor suppressor and promoter. The complexity of senescence in cancer arises from its mechanistic diversity, potential reversibility, and heterogeneity. A key mediator of these effects is the senescence-associated secretory phenotype (SASP), a repertoire of bioactive molecules that influence tumor microenvironment (TME) remodeling, modulate cancer cell behavior, and contribute to therapeutic resistance. Given its intricate role in cancer biology, senescence presents both challenges and opportunities for therapeutic intervention. Strategies targeting senescence pathways, including senescence-inducing therapies and senolytic approaches, offer promising avenues for cancer treatment. This review provides a comprehensive analysis of the regulatory mechanisms governing cellular senescence in tumors. We also discuss emerging strategies to modulate senescence, highlighting novel therapeutic opportunities. A deeper understanding of these processes is essential for developing precision therapies and improving clinical outcomes.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"25 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757997","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
Wnt signaling in cancer: from biomarkers to targeted therapies and clinical translation
IF 37.3 1区 医学
Molecular Cancer Pub Date : 2025-04-02 DOI: 10.1186/s12943-025-02306-w
Muhammad Tufail, Can-Hua Jiang, Ning Li
{"title":"Wnt signaling in cancer: from biomarkers to targeted therapies and clinical translation","authors":"Muhammad Tufail, Can-Hua Jiang, Ning Li","doi":"10.1186/s12943-025-02306-w","DOIUrl":"https://doi.org/10.1186/s12943-025-02306-w","url":null,"abstract":"The Wnt signaling pathway plays a crucial role in development and tissue homeostasis, regulating key cellular processes such as proliferation, differentiation, and apoptosis. However, its abnormal activation is strongly associated with tumorigenesis, metastasis, and resistance to therapy, making it a vital target for cancer treatment. This review provides a comprehensive insight into the role of Wnt signaling in cancer, examining its normal physiological functions, dysregulation in malignancies, and therapeutic potential. We emphasize the importance of predicting Wnt signaling sensitivity and identify key biomarkers across various cancer types. Additionally, we address the challenges and future prospects of Wnt-targeted therapies, including biomarker discovery, advancements in emerging technologies, and their application in clinical practice.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"3 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757996","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: Tetrathiomolybdate inhibits head and neck cancer metastasis by decreasing tumor cell motility, invasiveness and by promoting tumor cell anoikis
IF 37.3 1区 医学
Molecular Cancer Pub Date : 2025-04-01 DOI: 10.1186/s12943-025-02316-8
Pawan Kumar, Arti Yadav, Samip N. Patel, Mozaffarul Islam, Quintin Pan, Sofia D. Merajver, Theodoros N. Teknos
{"title":"Retraction Note: Tetrathiomolybdate inhibits head and neck cancer metastasis by decreasing tumor cell motility, invasiveness and by promoting tumor cell anoikis","authors":"Pawan Kumar, Arti Yadav, Samip N. Patel, Mozaffarul Islam, Quintin Pan, Sofia D. Merajver, Theodoros N. Teknos","doi":"10.1186/s12943-025-02316-8","DOIUrl":"https://doi.org/10.1186/s12943-025-02316-8","url":null,"abstract":"<p><b>Retraction Note: </b><b><i>Mol Cancer </i></b><b>9, 206 (2010)</b></p><p><b>https://doi.org/10.1186/1476-4598-9-206</b></p><p>The Editor-in-Chief has retracted this article. After publication, concerns were raised regarding highly similar images between this article and the authors’ earlier publication [1]. Specifically, Fig. 5A TM- image in this article appears to overlap with Fig. 6C UM-SCC-74 A + EC-Bcl-2 in [1], and Fig. 5A TM + image appears to overlap with Fig. 6C UM-SCC-74 A + EC-VC and UM-SCC-74 A + EC-Bcl-2 + α-IL-8 images in [1]. In addition, Fig. 1C EC-VC + TM and EC-Bcl-2 + TM images appear to overlap.</p><p>The Editor-in-Chief therefore no longer has confidence in the presented data.</p><p>The authors have not responded to any correspondence from the editor or publisher about this retraction.</p><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Kumar P, Ning Y, Polverini PJ. Endothelial cells expressing Bcl-2 promotes tumor metastasis by enhancing tumor angiogenesis, blood vessel leakiness and tumor invasion. Lab Invest. 2008;88(7):740–9. https://doi.org/10.1038/labinvest.2008.46.</p><p>Article CAS PubMed Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><h3>Authors and Affiliations</h3><ol><li><p>Department of Otolaryngology-Head and Neck Surgery and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA</p><p>Pawan Kumar, Arti Yadav, Mozaffarul Islam, Quintin Pan & Theodoros N. Teknos</p></li><li><p>Department of Otolaryngology-Head and Neck Surgery, University of South Florida, Tampa, FL, USA</p><p>Samip N. Patel</p></li><li><p>Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann, Arbor, MI, USA</p><p>Sofia D. Merajver</p></li></ol><span>Authors</span><ol><li><span>Pawan Kumar</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Arti Yadav</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Samip N. Patel</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Mozaffarul Islam</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Quintin Pan</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Sofia D. Merajver</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></l","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"37 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744871","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
C1Q+ TPP1+ macrophages promote colon cancer progression through SETD8-driven p53 methylation
IF 37.3 1区 医学
Molecular Cancer Pub Date : 2025-03-31 DOI: 10.1186/s12943-025-02293-y
Veronica Veschi, Francesco Verona, Sebastiano Di Bella, Alice Turdo, Miriam Gaggianesi, Simone Di Franco, Laura Rosa Mangiapane, Chiara Modica, Melania Lo Iacono, Paola Bianca, Ornella Roberta Brancato, Caterina D’Accardo, Gaetana Porcelli, Vincenzo Luca Lentini, Isabella Sperduti, Elisabetta Sciacca, Peter Fitzgerald, David Lopez-Perez, Pierre Martine, Kate Brown, Giuseppe Giannini, Ettore Appella, Giorgio Stassi, Matilde Todaro
{"title":"C1Q+ TPP1+ macrophages promote colon cancer progression through SETD8-driven p53 methylation","authors":"Veronica Veschi, Francesco Verona, Sebastiano Di Bella, Alice Turdo, Miriam Gaggianesi, Simone Di Franco, Laura Rosa Mangiapane, Chiara Modica, Melania Lo Iacono, Paola Bianca, Ornella Roberta Brancato, Caterina D’Accardo, Gaetana Porcelli, Vincenzo Luca Lentini, Isabella Sperduti, Elisabetta Sciacca, Peter Fitzgerald, David Lopez-Perez, Pierre Martine, Kate Brown, Giuseppe Giannini, Ettore Appella, Giorgio Stassi, Matilde Todaro","doi":"10.1186/s12943-025-02293-y","DOIUrl":"https://doi.org/10.1186/s12943-025-02293-y","url":null,"abstract":"In many tumors, the tumor suppressor TP53 is not mutated, but functionally inactivated. However, mechanisms underlying p53 functional inactivation remain poorly understood. SETD8 is the sole enzyme known to mono-methylate p53 on lysine 382 (p53K382me1), resulting in the inhibition of its pro-apoptotic and growth-arresting functions. We analyzed SETD8 and p53K382me1 expression in clinical colorectal cancer (CRC) and inflammatory bowel disease (IBD) samples. Histopathological examinations, RNA sequencing, ChIP assay and preclinical in vivo CRC models, were used to assess the functional role of p53 inactivation in tumor cells and immune cell infiltration. By integrating bulk RNAseq and scRNAseq approaches in CRC patients, SETD8-mediated p53 regulation resulted the most significantly enriched pathway. p53K382me1 expression was confined to colorectal cancer stem cells (CR-CSCs) and C1Q+ TPP1+ tumor-associated macrophages (TAMs) in CRC patient tissues, with high levels predicting decreased survival probability. TAMs promote p53 functional inactivation in CR-CSCs through IL-6 and MCP-1 secretion and increased levels of CEBPD, which directly binds SETD8 promoter thus enhancing its transcription. The direct binding of C1Q present on macrophages and C1Q receptor (C1QR) present on cancer stem cells mediates the cross-talk between the two cell compartments. As monotherapy, SETD8 genetic and pharmacological (UNC0379) inhibition affects the tumor growth and metastasis formation in CRC mouse avatars, with enhanced effects observed when combined with IL-6 receptor targeting. These findings suggest that p53K382me1 may be an early step in tumor initiation, especially in inflammation-induced CRC, and could serve as a functional biomarker and therapeutic target in adjuvant setting for advanced CRCs. ","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"183 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736599","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
Correction: SPOCK1 as a potential cancer prognostic marker promotes the proliferation and metastasis of gallbladder cancer cells by activating the PI3K/AKT pathway
IF 37.3 1区 医学
Molecular Cancer Pub Date : 2025-03-31 DOI: 10.1186/s12943-025-02313-x
Yi-Jun Shu, Hao Weng, Yuan-Yuan Ye, Yun-Ping Hu, Run-Fa Bao, Yang Cao, Xu-An Wang, Fei Zhang, Shan-Shan Xiang, Huai-Feng Li, Xiang-Song Wu, Mao-Lan Li, Lin Jiang, Wei Lu, Bao-San Han, Zhi-Gang Jie, Ying-Bin Liu
{"title":"Correction: SPOCK1 as a potential cancer prognostic marker promotes the proliferation and metastasis of gallbladder cancer cells by activating the PI3K/AKT pathway","authors":"Yi-Jun Shu, Hao Weng, Yuan-Yuan Ye, Yun-Ping Hu, Run-Fa Bao, Yang Cao, Xu-An Wang, Fei Zhang, Shan-Shan Xiang, Huai-Feng Li, Xiang-Song Wu, Mao-Lan Li, Lin Jiang, Wei Lu, Bao-San Han, Zhi-Gang Jie, Ying-Bin Liu","doi":"10.1186/s12943-025-02313-x","DOIUrl":"https://doi.org/10.1186/s12943-025-02313-x","url":null,"abstract":"<p><b>Correction: Mol Cancer 14, 12 (2015)</b></p><p><b>https://doi.org/10.1186/s12943-014-0276-y</b></p><br/><p>Following publication of the original article [1], the author has requested the publication of an erratum to address the following issues stated below.</p><p>Recently, in planning and designing further studies of the roles of SPOCK1 in chemo-resistance of gallbladder cancer, based on the authors ‘ previous investigations including the above mentioned paper, they noticed an error in the Fig. 5 A&B. They found that in Fig. 5A, the pictures of NOZ cells in the shSPOCK1 group were placed incorrectly and in Fig. 5B, the pictures of SGC cells in the Mock group were placed incorrectly. There errors likely resulted from incorporation of the incorrect figure panels due to the high similarities of both file names and images from the repeated experiments in the original data folder. However, these errors in the images do not affect any statistical results and the relevant conclusions. They have carefully examined the original results and now the incorrect Fig. 5 and correct Fig. 5 are povided below.</p><p>Incorrect Fig. 5:</p><figure><figcaption><b data-test=\"figure-caption-text\">Fig. 5</b></figcaption><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02313-x/MediaObjects/12943_2025_2313_Fig1_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure 1\" aria-describedby=\"Fig1\" height=\"1016\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02313-x/MediaObjects/12943_2025_2313_Fig1_HTML.png\" width=\"685\"/></picture><p>SPOCK1 promotes tumor invasion and metastasis <i>in vitro</i> by inducing EMT.<b> A</b> Wound closure was delayed in Lv-shSPOCK1-transduced cells compared with that in CTRL and Lv-shNC cells at 48 h in both GBC-SD and NOZ cells. Overexpression of SPOCK1 in SGC-996 cells had the opposite effects (*<i>P</i> < 0.05, *<i>*P</i> < 0.01, and ***<i>P</i> < 0.001). <b>B</b> Matrigel invasion assay of CTRL, Lv-shNC, Lv-shSPOCK1, MOCK, and SPOCK1 transfectants cells. The number of invaded cells was calculated and is depicted in the bar chart. (*<i>P</i> < 0.05, **<i>P</i> < 0.01, and ***<i>P</i> < 0.001). <b>C </b>and<b> D</b> The protein expression of Snail, vimentin, N-cadherin and E-cadherin in the indicated cells was examined by western blotting. The protein expression of vementin and E-cadherin was examined by immunofluorescence analysis. The red signal represents staining for E-cadherin or vimentin. Nuclei were counterstained with DAPI</p><span>Full size image</span><svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-chevron-right-small\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></figure><p>Correct Fig. 5:</p><figure><figcaption><b data-test=\"figure-caption-text\">Fig. 5</b></figcaption><picture><source srcset=\"//media.springernature.com/lw685/springe","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"38 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736603","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}
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