Molecular Cancer最新文献

{"title":"BIRC2 blockade facilitates immunotherapy of hepatocellular carcinoma","authors":"Lingyi Fu, Shuo Li, Jie Mei, Ziteng Li, Xia Yang, Chengyou Zheng, Nai Li, Yansong Lin, Chao Cao, Lixuan Liu, Liyun Huang, Xiujiao Shen, Yuhua Huang, Jingping Yun","doi":"10.1186/s12943-025-02319-5","DOIUrl":"https://doi.org/10.1186/s12943-025-02319-5","url":null,"abstract":"The effectiveness of immunotherapy in hepatocellular carcinoma (HCC) is limited, however, the molecular mechanism remains unclear. In this study, we identified baculoviral IAP repeat-containing protein 2 (BIRC2) as a key regulator involved in immune evasion of HCC. Genome-wide CRISPR/Cas9 screening was conducted to identify tumor-intrinsic genes pivotal for immune escape. In vitro and in vivo models demonstrated the role of BIRC2 in protecting HCC cells from immune killing. Then the function and relevant signaling pathways of BIRC2 were explored. The therapeutic efficacy of BIRC2 inhibitor was examined in different in situ and xenograft HCC models. Elevated expression of BIRC2 correlated with adverse prognosis and resistance to immunotherapy in HCC patients. Mechanistically, BIRC2 interacted with and promoted the ubiquitination-dependent degradation of NFκB-inducing kinase (NIK), leading to the inactivation of the non-canonical NFκB signaling pathway. This resulted in the decrease of major histocompatibility complex class I (MHC-I) expression, thereby protecting HCC cells from T cell-mediated cytotoxicity. Silencing BIRC2 using shRNA or inhibiting it with small molecules increased the sensitivity of HCC cells to immune killing. Meanwhile, BIRC2 blockade improved the function of T cells both in vitro and in vivo. Targeting BIRC2 significantly inhibited tumor growth, and enhanced the efficacy of anti-programmed death protein 1 (PD-1) therapy. Our findings suggested that BIRC2 blockade facilitated immunotherapy of HCC by simultaneously sensitizing tumor cells to immune attack and boosting the anti-tumor immune response of T cells.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"183 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827663","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":"KF1601, a dual inhibitor of BCR::ABL1 and FLT3, overcomes drug resistance in FLT3+ blast phase chronic myeloid leukemia","authors":"Hyun-Jin Kwon, Ji Eun Shin, Amir Khan, So Yeon Park, Jiyoung Kim, Jee-Young Lee, Doohyun Lee, Seungyeon Lee, Chun Young Im, Heegyum Moon, Ye Ri Han, Minori Tamai, Koshi Akahane, Takeshi Inukai, Wonhwa Lee, Hyelim Kim, Hong Nam Kim, Sung-Min Ahn, Hyun Woo Park, Dong-Wook Kim","doi":"10.1186/s12943-025-02292-z","DOIUrl":"https://doi.org/10.1186/s12943-025-02292-z","url":null,"abstract":"Blast phase chronic myeloid leukemia (BP-CML) poses significant clinical challenges due to its drug resistance, resulting from BCR::ABL1-dependent mutations and BCR::ABL1-independent pathways. Previously, we reported that FLT3 pathway is activated in ~ 50% of BP-CML cases, indicating a potential avenue for therapeutic intervention via dual inhibition of BCR::ABL1 and FLT3. Here, we aimed to evaluate the efficacy of KF1601, a dual inhibitor of BCR::ABL1 and FLT3, in overcoming drug resistance in BP-CML while also comparing its thrombo-inflammatory responses with those of ponatinib, known to have severe cardiovascular adverse events in human. Our findings revealed that KF1601 effectively inhibited of BCR::ABL1 signaling pathway, even in the presence of the T315I mutation. KF1601 achieved complete tumor regression in K562 xenograft mouse models, and prolonged survival significantly in orthotopic mouse models. Furthermore, KF1601 effectively inhibited the FLT3 signaling pathway in imatinib-resistant K562 cells expressing FLT3 and TAZ, suppressing cell proliferation through dual inhibition of BCR::ABL1 and FLT3. These findings were corroborated using drug-resistant BP-CML cells from patients. In assessing thrombo-inflammatory responses using a murine thrombosis model, ponatinib induced severe responses, leading to carotid artery occlusion and extensive vessel wall damage. In contrast, in mice treated with KF1601, carotid arteries remained unoccluded, with vessel walls preserved intact. In summary, KF1601 demonstrated promising preclinical efficacy in overcoming resistance mechanisms, including the BCR::ABL1T315I mutation, while also addressing FLT3 signaling implicated in BP-CML progression. Unlike existing therapies such as ponatinib, KF1601 offers a favorable safety profile, potentially minimizing the risk of life-threatening adverse effects.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"7 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827661","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":"Editorial expression of concern: Yin Yang-1 suppresses invasion and metastasis of pancreatic ductal adenocarcinoma by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism","authors":"Jing-Jing Zhang, Yi Zhu, Kun-Ling Xie, Yun-Peng Peng, Jin-Qiu Tao, Jie Tang, Zheng Li, Ze-Kuan Xu, Cun-Cai Dai, Zhu-Yin Qian, Kui-Rong Jiang, Jun-Li Wu, Wen-Tao Gao, Qing Du, Yi Miao","doi":"10.1186/s12943-025-02326-6","DOIUrl":"https://doi.org/10.1186/s12943-025-02326-6","url":null,"abstract":"<p><b>Correction: Mol Cancer 13, 130 (2014)</b></p><p>https://doi.org/10.1186/1476-4598-13-130</p><p>The Editor-in-Chief is issuing an editorial expression of concern to alert readers that after the publication of this article, it was brought to the attention of the publisher that there are a number of image integrity concerns. There appear to be high similarities between Fig. 1e GAPDH and Fig. 3b GAPDH, representing different conditions. Figure 3d Invasion-BXPC-YY1 appears to partially overlap with Fig. 3d Migration-BXPC-Scramble shRNA. Figure 5a Erk1/2-Vector and Fig. 5a p-Erk1/2-YY1 shRNA also appear to be highly similar. The authors were able to provide the original cell images for Fig. 3d, but were unable to provide the original images for any of the blots. Readers are urged to take caution when interpreting the content and conclusions of this article.</p><p>Authors Jing-Jing Zhang. Yun-Peng Peng, Yi Miao, Kun-Ling Xie, and Yi Zhu agree with this Editorial Expression of Concern. All other authors have not responded to correspondence from the publisher regarding this Editorial Expression of Concern.</p><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Zhang JJ, Zhu Y, Xie KL, et al. Yin Yang-1 suppresses invasion and metastasis of pancreatic ductal adenocarcinoma by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism. Mol Cancer. 2014;13:130. https://doi.org/10.1186/1476-4598-13-130.</p><p>Article PubMed PubMed Central CAS 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 General Surgery, Jiangsu Province Academy of Clinical Medicine, Institute of Tumor Biology, The first Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China</p><p>Jing-Jing Zhang, Yi Zhu, Ze-Kuan Xu, Cun-Cai Dai, Zhu-Yin Qian, Kui-Rong Jiang, Jun-Li Wu, Wen-Tao Gao, Qing Du & Yi Miao</p></li><li><p>Jiangsu Province Academy of Clinical Medicine, Institute of Tumor Biology, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China</p><p>Jing-Jing Zhang, Yi Zhu, Ze-Kuan Xu, Qing Du & Yi Miao</p></li><li><p>The First School of Clinical Medicine, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, People’s Republic of China</p><p>Kun-Ling Xie, Yun-Peng Peng, Jin-Qiu Tao, Jie Tang & Zheng Li</p></li></ol><span>Authors</span><ol><li><span>Jing-Jing Zhang</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>Yi Zhu</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>Kun-Ling Xie</span>View auth","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"60 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827638","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":"Correction: CMTM6 overexpression confers trastuzumab resistance in HER2‑positive breast cancer","authors":"Fei Xing, Hongli Gao, Guanglei Chen, Lisha Sun, Jiayi Sun, Xinbo Qiao, Jinqi Xue, Caigang Liu","doi":"10.1186/s12943-025-02317-7","DOIUrl":"https://doi.org/10.1186/s12943-025-02317-7","url":null,"abstract":"<p>\u0000<b>Correction</b><b>: </b>\u0000<b>Mol Cancer 22, 6 (2023)</b>\u0000</p><p>\u0000<b>https://doi.org/10.1186/s12943-023–01716-y</b>\u0000</p><p>Following publication of the original article [1], the authors sincerely acknowledge that an incorrect image panel was inadvertently included in Figure 3F and 4H. To ensure the accuracy and integrity of the article, the authors have carefully reviewed the original data and replaced the erroneous images. This correction does not affect the main findings or conclusions of the study. The revised figures and their corresponding correct captions are provided below.</p><p>Incorrect Fig. 3 and incorrect caption:</p><figure><figcaption><b data-test=\"figure-caption-text\">Fig. 3</b></figcaption><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02317-7/MediaObjects/12943_2025_2317_Fig1_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure 1\" aria-describedby=\"Fig1\" height=\"874\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02317-7/MediaObjects/12943_2025_2317_Fig1_HTML.png\" width=\"685\"/></picture><p>CMTM6 promotes the survival, migration, invasion and trastuzumab resistance of BC cells in vitro<i>. </i><b>A</b> qRT-PCR and Western blot validated CMTM6 silencing in JIMT-1 cells and CMTM6-overexpresstion in SKBR3 cells. Negative control (NC) JIMT-1 and SKBR3 cells were transduced with lentivirus for the control shRNA or transfected with the control plasmid, respectively. <b>B, C</b> CCK-8 assay determined the viability of the indicated BC cells following treatment with trastuzumab (0–100 μg/ml). <b>D, E</b> ethynyl-2′-deoxyuridine (EdU) analysis of the proliferation of CMTM6-silenced JIMT-1 cells, CMTM6 overexpressing SKBR3 cells, control JIMT-1 cells and SKBR3 cells following treatment with trastuzumab (10 μg/ml). (scale bar, 50 μM). <b>F, G</b> TUNEL analysis of apoptotic CMTM6-silenced JIMT-1 cells, CMTM6 overexpressing SKBR3 cells, control JIMT-1 and SKBR3 cells following treatment with trastuzumab (10 μg/ml). <b>H, I</b> Cell invasion assay revealed that CMTM6 silencing inhibited JIMT-1 cell invasion while CMTM6 overexpression enhanced SKBR3 cell invasion following treatment with trastuzumab (10 μg/ml). (scale bar, 50 μM). Data are representative images or expressed as the mean ± SD of each group from three independent experiments. *<i>P</i> < 0.05; **<i>P</i> < 0.01; ***<i>P</i> < 0.001</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. 3 and correct caption:</p><figure><figcaption><b data-test=\"figure-caption-text\">Fig. 3</b></figcaption><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02317-7/MediaObjects/12943_2025_2317_Fig2_HTML.png?as=webp\" type=\"image/webp\"/><img ","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"37 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827658","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":"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}

{"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}

{"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}

{"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}

{"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}

{"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}