Molecular Cancer最新文献

{"title":"Discovery of vitexin as a novel VDR agonist that mitigates the transition from chronic intestinal inflammation to colorectal cancer","authors":"Yonger Chen, Jian Liang, Shuxian Chen, Nan Lin, Shuoxi Xu, Jindian Miao, Jing Zhang, Chen Chen, Xin Yuan, Zhuoya Xie, Enlin Zhu, Mingsheng Cai, Xiaoli Wei, Shaozhen Hou, Hailin Tang","doi":"10.1186/s12943-024-02108-6","DOIUrl":"https://doi.org/10.1186/s12943-024-02108-6","url":null,"abstract":" Colitis-associated colorectal cancer (CAC) frequently develops in patients with inflammatory bowel disease (IBD) who have been exposed to a prolonged state of chronic inflammation. The investigation of pharmacological agents and their mechanisms to prevent precancerous lesions and inhibit their progression remains a significant focus and challenge in CAC research. Previous studies have demonstrated that vitexin effectively mitigates CAC, however, its precise mechanism of action warrants further exploration. This study reveals that the absence of the Vitamin D receptor (VDR) accelerates the progression from chronic colitis to colorectal cancer. Our findings indicate that vitexin can specifically target the VDR protein, facilitating its translocation into the cell nucleus to exert transcriptional activity. Additionally, through a co-culture model of macrophages and cancer cells, we observed that vitexin promotes the polarization of macrophages towards the M1 phenotype, a process that is dependent on VDR. Furthermore, ChIP-seq analysis revealed that vitexin regulates the transcriptional activation of phenazine biosynthesis-like domain protein (PBLD) via VDR. ChIP assays and dual luciferase reporter assays were employed to identify the functional PBLD regulatory region, confirming that the VDR/PBLD pathway is critical for vitexin-mediated regulation of macrophage polarization. Finally, in a mouse model with myeloid VDR gene knockout, we found that the protective effects of vitexin were abolished in mid-stage CAC. In summary, our study establishes that vitexin targets VDR and modulates macrophage polarization through the VDR/PBLD pathway, thereby alleviating the transition from chronic colitis to colorectal cancer. ","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"63 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174528","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: Identification of miPEP133 as a novel tumor-suppressor microprotein encoded by miR-34a pri-miRNA","authors":"Min Kang, Bo Tang, Jixi Li, Ziyan Zhou, Kang Liu, Rensheng Wang, Ziyan Jiang, Fangfang Bi, David Patrick, Dongin Kim, Anirban K. Mitra, Yang Yang-Hartwich","doi":"10.1186/s12943-024-02111-x","DOIUrl":"https://doi.org/10.1186/s12943-024-02111-x","url":null,"abstract":"<p><b>Correction: Mol Cancer 19, 143 (2020)</b></p><p><b>https://doi.org/10.1186/s12943-020-01248-9</b></p><p>Recently in a re-examination of our previously published paper [1], “Identification of miPEP133 as a novel tumor-suppressor microprotein encoded by miR-34a pri-miRNA” [Molecular Cancer 19, article number 143 (2020)], we found two errors.</p><p>The first error is that we presented the wrong primer sequences for GAPDH in the Supplemental Methods (in the Additional file 2). We mistakenly listed the primer sequences for human β-actin (<i>ACTB</i>) as for GAPDH. The correct primer sequences for GAPDH are 5′-AATGAAGGGGTCATTGATGG − 3′ and 5′-AAGGTGAAGGTCGGAGTCAA − 3′. These were used in this study. Please find the resized Additional file 2 in the attachment.</p><p>The other error is a misplaced western blot image for the loading control β-actin in Fig. 4e. We have identified the correct image for β-actin bands. The following is the corrected figure.</p><figure><picture><img alt=\"figure a\" aria-describedby=\"Figa\" height=\"889\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-024-02111-x/MediaObjects/12943_2024_2111_Fig1_HTML.png\" width=\"685\"/></picture></figure><p>They are minor errors, and their correction does not affect the conclusion of this article, however, we sincerely apologize to the readers and editors for the inconvenience caused by our mistakes. We would like to ask for an opportunity to publish this correction.</p><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Kang M, Tang B, Li J, et al. Identification of miPEP133 as a novel tumor-suppressor microprotein encoded by miR-34a pri-miRNA. Mol Cancer. 2020;19:143. https://doi.org/10.1186/s12943-020-01248-9.</p><p>Article CAS PubMed PubMed Central 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>The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, China</p><p>Min Kang, Bo Tang, Jixi Li, Ziyan Zhou & Kang Liu</p></li><li><p>Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, 06510, USA</p><p>Min Kang, Ziyan Jiang, Fangfang Bi, David Patrick & Yang Yang-Hartwich</p></li><li><p>Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China</p><p>Min Kang & Rensheng Wang</p></li><li><p>Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China</p><p>Bo Tang</p></li><li><p>The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China</p><p>Ziyan Jiang</p></li><li><p>Sheng Jing Hospital of China Medical","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"57 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170752","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: Prostate cancer-associated SPOP mutations enhance cancer cell survival and docetaxel resistance by upregulating Caprin1-dependent stress granule assembly","authors":"Qing Shi, Yasheng Zhu, Jian Ma, Kun Chang, Dongling Ding, Yang Bai, Kun Gao, Pingzhao Zhang, Ren Mo, Kai Feng, Xiaying Zhao, Liang Zhang, Huiru Sun, Dongyue Jiao, Yingji Chen, Yinghao Sun, Shi-min Zhao, Haojie Huang, Yao Li, Shancheng Ren, Chenji Wang","doi":"10.1186/s12943-024-02112-w","DOIUrl":"https://doi.org/10.1186/s12943-024-02112-w","url":null,"abstract":"<p><b>Correction</b><b>: </b><b>Mol Cancer 18, 170 (2019)</b></p><p><b>https://doi.org/10.1186/s12943-019-1096-x</b></p><br/><p>The authors apologize for the errors in Fig. 2. In the original published version [1], the western blot image of Actin in Fig. 2D was mistakenly uploaded. The Western blot image of BRD4 in Fig. 2G was mistakenly uploaded. The Western blot one lane of FLAG (Input) in Fig. 2K was inadvertently omitted due to a careless mistake. The correct figure is shown below.</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-024-02112-w/MediaObjects/12943_2024_2112_Figa_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure a\" aria-describedby=\"Figa\" height=\"544\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-024-02112-w/MediaObjects/12943_2024_2112_Figa_HTML.png\" width=\"685\"/></picture></figure><p>The authors apologize for the errors in Fig. 3. In the original published version, the Western blot image of Myc (Input) in Fig. 3A was mistakenly uploaded. The Western blot image of Myc (Input) in Fig. 3C was mistakenly uploaded. The Western blot image of FLAG in Fig. 3D was mistakenly uploaded. The correct figure is shown below.</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-024-02112-w/MediaObjects/12943_2024_2112_Figb_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure b\" aria-describedby=\"Figb\" height=\"655\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-024-02112-w/MediaObjects/12943_2024_2112_Figb_HTML.png\" width=\"685\"/></picture></figure><p>The authors apologize for two errors in Supplementary Figure 1. In the original published version, the Western blot image of FLAG (Input) in Supplementary Figure 1C was mistakenly uploaded. The Western blot image of FLAG (Input) in Supplementary Figure 1E was mistakenly uploaded. The correct figure is shown below.</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-024-02112-w/MediaObjects/12943_2024_2112_Figc_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure c\" aria-describedby=\"Figc\" height=\"562\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-024-02112-w/MediaObjects/12943_2024_2112_Figc_HTML.png\" width=\"685\"/></picture></figure><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Shi Q, Zhu Y, Ma J, et al. Prostate Cancer-associated SPOP mutations enhance cancer cell survival and docetaxel resistance by upregulating Caprin1-dependent stress granule assembly. Mol Cancer. 2019;18:170. https://doi.org/10.1186/s12943-019-1096-x.</p><p>Article CAS PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use x","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"43 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166195","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":"Phenotypic and spatial heterogeneity of CD8+ tumour infiltrating lymphocytes","authors":"Yikan Sun, Eloy Yinwang, Shengdong Wang, Zenan Wang, Fangqian Wang, Yucheng Xue, Wenkan Zhang, Shenzhi Zhao, Haochen Mou, Shixin Chen, Lingxiao Jin, Binghao Li, Zhaoming Ye","doi":"10.1186/s12943-024-02104-w","DOIUrl":"https://doi.org/10.1186/s12943-024-02104-w","url":null,"abstract":"CD8+ T cells are the workhorses executing adaptive anti-tumour response, and targets of various cancer immunotherapies. Latest advances have unearthed the sheer heterogeneity of CD8+ tumour infiltrating lymphocytes, and made it increasingly clear that the bulk of the endogenous and therapeutically induced tumour-suppressive momentum hinges on a particular selection of CD8+ T cells with advantageous attributes, namely the memory and stem-like exhausted subsets. A scrutiny of the contemporary perception of CD8+ T cells in cancer and the subgroups of interest along with the factors arbitrating their infiltration contextures, presented herein, may serve as the groundwork for future endeavours to probe further into the regulatory networks underlying their differentiation and migration, and optimise T cell-based immunotherapies accordingly.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"1 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158812","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":"Advances on immunotherapy for osteosarcoma.","authors":"Shengnan Yu, Xudong Yao","doi":"10.1186/s12943-024-02105-9","DOIUrl":"10.1186/s12943-024-02105-9","url":null,"abstract":"<p><p>Osteosarcoma is the most common primary bone cancer in children and young adults. Limited progress has been made in improving the survival outcomes in patients with osteosarcoma over the past four decades. Especially in metastatic or recurrent osteosarcoma, the survival rate is extremely unsatisfactory. The treatment of osteosarcoma urgently needs breakthroughs. In recent years, immunotherapy has achieved good therapeutic effects in various solid tumors. Due to the low immunogenicity and immunosuppressive microenvironment of osteosarcoma, immunotherapy has not yet been approved in osteosarcoma patients. However, immune-based therapies, including immune checkpoint inhibitors, chimeric antigen receptor T cells, and bispecfic antibodies are in active clinical development. In addition, other immunotherapy strategies including modified-NK cells/macrophages, DC vaccines, and cytokines are still in the early stages of research, but they will be hot topics for future study. In this review, we showed the functions of cell components including tumor-promoting and tumor-suppressing cells in the tumor microenvironment of osteosarcoma, and summarized the preclinical and clinical research results of various immunotherapy strategies in osteosarcoma, hoping to provide new ideas for future research in this field.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"23 1","pages":"192"},"PeriodicalIF":27.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11382402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer therapy resistance mediated by cancer-associated fibroblast-derived extracellular vesicles: biological mechanisms to clinical significance and implications","authors":"Zhengjun Lin, Guoqing Li, Ke Jiang, Zhihong Li, Tang Liu","doi":"10.1186/s12943-024-02106-8","DOIUrl":"https://doi.org/10.1186/s12943-024-02106-8","url":null,"abstract":"Cancer-associated fibroblasts (CAFs) are a diverse stromal cell population within the tumour microenvironment, where they play fundamental roles in cancer progression and patient prognosis. Multiple lines of evidence have identified that CAFs are critically involved in shaping the structure and function of the tumour microenvironment with numerous functions in regulating tumour behaviours, such as metastasis, invasion, and epithelial-mesenchymal transition (EMT). CAFs can interact extensively with cancer cells by producing extracellular vesicles (EVs), multiple secreted factors, and metabolites. Notably, CAF-derived EVs have been identified as critical mediators of cancer therapy resistance, and constitute novel therapy targets and biomarkers in cancer management. This review aimed to summarize the biological roles and detailed molecular mechanisms of CAF-derived EVs in mediating cancer resistance to chemotherapy, targeted therapy agents, radiotherapy, and immunotherapy. We also discussed the therapeutic potential of CAF-derived EVs as novel targets and clinical biomarkers in cancer clinical management, thereby providing a novel therapeutic strategy for enhancing cancer therapy efficacy and improving patient prognosis.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"9 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144325","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":"Biomarkers for diagnosis and therapeutic options in hepatocellular carcinoma","authors":"Yau-Tuen Chan, Cheng Zhang, Junyu Wu, Pengde Lu, Lin Xu, Hongchao Yuan, Yibin Feng, Zhe-Sheng Chen, Ning Wang","doi":"10.1186/s12943-024-02101-z","DOIUrl":"https://doi.org/10.1186/s12943-024-02101-z","url":null,"abstract":"Liver cancer is a global health challenge, causing a significant social-economic burden. Hepatocellular carcinoma (HCC) is the predominant type of primary liver cancer, which is highly heterogeneous in terms of molecular and cellular signatures. Early-stage or small tumors are typically treated with surgery or ablation. Currently, chemotherapies and immunotherapies are the best treatments for unresectable tumors or advanced HCC. However, drug response and acquired resistance are not predictable with the existing systematic guidelines regarding mutation patterns and molecular biomarkers, resulting in sub-optimal treatment outcomes for many patients with atypical molecular profiles. With advanced technological platforms, valuable information such as tumor genetic alterations, epigenetic data, and tumor microenvironments can be obtained from liquid biopsy. The inter- and intra-tumoral heterogeneity of HCC are illustrated, and these collective data provide solid evidence in the decision-making process of treatment regimens. This article reviews the current understanding of HCC detection methods and aims to update the development of HCC surveillance using liquid biopsy. Recent critical findings on the molecular basis, epigenetic profiles, circulating tumor cells, circulating DNAs, and omics studies are elaborated for HCC diagnosis. Besides, biomarkers related to the choice of therapeutic options are discussed. Some notable recent clinical trials working on targeted therapies are also highlighted. Insights are provided to translate the knowledge into potential biomarkers for detection and diagnosis, prognosis, treatment response, and drug resistance indicators in clinical practice.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"19 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142518","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":"Acyl-coenzyme a binding protein (ACBP) - a risk factor for cancer diagnosis and an inhibitor of immunosurveillance","authors":"Léa Montégut, Peng Liu, Liwei Zhao, María Pérez-Lanzón, Hui Chen, Misha Mao, Shuai Zhang, Lisa Derosa, Julie Le Naour, Flavia Lambertucci, Silvia Mingoia, Uxía Nogueira-Recalde, Rafael Mena-Osuna, Irene Herranz-Montoya, Nabil Djouder, Sylvain Baulande, Hui Pan, Adrien Joseph, Meriem Messaoudene, Bertrand Routy, Marine Fidelle, Tarek Ben Ahmed, Olivier Caron, Pierre Busson, David Boulate, Mélanie Deschasaux-Tanguy, Nathalie Arnault, Jonathan G. Pol, Eliane Piaggio, Mathilde Touvier, Laurence Zitvogel, Suzette Delaloge, Isabelle Martins, Guido Kroemer","doi":"10.1186/s12943-024-02098-5","DOIUrl":"https://doi.org/10.1186/s12943-024-02098-5","url":null,"abstract":"The plasma concentrations of acyl coenzyme A binding protein (ACBP, also known as diazepam-binding inhibitor, DBI, or ‘endozepine’) increase with age and obesity, two parameters that are also amongst the most important risk factors for cancer. We measured ACBP/DBI in the plasma from cancer-free individuals, high-risk patients like the carriers of TP53 or BRCA1/2 mutations, and non-syndromic healthy subjects who later developed cancer. In mice, the neutralization of ACBP/DBI was used in models of non-small cell lung cancer (NSCLC) and breast cancer development and as a combination treatment with chemoimmunotherapy (chemotherapy + PD-1 blockade) in the context of NSCLC and sarcomas. The anticancer T cell response upon ACBP/DBI neutralization was characterized by flow cytometry and single-cell RNA sequencing. Circulating levels of ACBP/DBI were higher in patients with genetic cancer predisposition (BRCA1/2 or TP53 germline mutations) than in matched controls. In non-syndromic cases, high ACBP/DBI levels were predictive of future cancer development, and especially elevated in patients who later developed lung cancer. In preclinical models, ACBP/DBI neutralization slowed down breast cancer and NSCLC development and enhanced the efficacy of chemoimmunotherapy in NSCLC and sarcoma models. When combined with chemoimmunotherapy, the neutralizing monoclonal antibody against ACBP/DBI reduced the frequency of regulatory T cells in the tumor bed, modulated the immune checkpoint profile, and increased activation markers. These findings suggest that ACBP/DBI acts as an endogenous immune suppressor. We conclude that elevation of ACBP/DBI constitutes a risk factor for the development of cancer and that ACBP/DBI is an actionable target for improving cancer immunosurveillance.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"381 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142540","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":"NAC1 promotes stemness and regulates myeloid-derived cell status in triple-negative breast cancer","authors":"Chrispus Ngule, Ruyi Shi, Xingcong Ren, Hongyan Jia, Felix Oyelami, Dong Li, Younhee Park, Jinhwan Kim, Hami Hemati, Yi Zhang, Xiaofang Xiong, Andrew Shinkle, Nathan L. Vanderford, Sara Bachert, Binhua P. Zhou, Jianlong Wang, Jianxun Song, Xia Liu, Jin-Ming Yang","doi":"10.1186/s12943-024-02102-y","DOIUrl":"https://doi.org/10.1186/s12943-024-02102-y","url":null,"abstract":"Triple negative breast cancer (TNBC) is a particularly lethal breast cancer (BC) subtype driven by cancer stem cells (CSCs) and an immunosuppressive microenvironment. Our study reveals that nucleus accumbens associated protein 1 (NAC1), a member of the BTB/POZ gene family, plays a crucial role in TNBC by maintaining tumor stemness and influencing myeloid-derived suppressor cells (MDSCs). High NAC1 expression correlates with worse TNBC prognosis. NAC1 knockdown reduced CSC markers and tumor cell proliferation, migration, and invasion. Additionally, NAC1 affects oncogenic pathways such as the CD44-JAK1-STAT3 axis and immunosuppressive signals (TGFβ, IL-6). Intriguingly, the impact of NAC1 on tumor growth varies with the host immune status, showing diminished tumorigenicity in natural killer (NK) cell-competent mice but increased tumorigenicity in NK cell-deficient ones. This highlights the important role of the host immune system in TNBC progression. In addition, high NAC1 level in MDSCs also supports TNBC stemness. Together, this study implies NAC1 as a promising therapeutic target able to simultaneously eradicate CSCs and mitigate immune evasion.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"7 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142519","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":"YTHDF2 in peritumoral hepatocytes mediates chemotherapy-induced antitumor immune responses through CX3CL1-mediated CD8⁺ T cell recruitment.","authors":"Zhenyun Yang, Xin Wang, Yizhen Fu, Weijie Wu, Zili Hu, Qingyang Lin, Wei Peng, Yangxun Pan, Juncheng Wang, Jinbin Chen, Dandan Hu, Zhongguo Zhou, Li Xu, Yaojun Zhang, Jiajie Hou, Minshan Chen","doi":"10.1186/s12943-024-02097-6","DOIUrl":"10.1186/s12943-024-02097-6","url":null,"abstract":"<p><p>Peritumoral hepatocytes are critical components of the liver cancer microenvironment, However, the role of peritumoral hepatocytes in the local tumor immune interface and the underlying molecular mechanisms have not been elucidated. YTHDF2, an RNA N⁶-methyladenosine (m⁶A) reader, is critical for liver tumor progression. The function and regulatory roles of YTHDF2 in peritumoral hepatocytes are unknown. This study demonstrated that oxaliplatin (OXA) upregulated m⁶A modification and YTHDF2 expression in hepatocytes. Studies using tumor-bearing liver-specific Ythdf2 knockout mice revealed that hepatocyte YTHDF2 suppresses liver tumor growth through CD8⁺ T cell recruitment and activation. Additionally, YTHDF2 mediated the response to immunotherapy. Mechanistically, OXA upregulated YTHDF2 expression by activating the cGAS-STING signaling pathway and consequently enhanced the therapeutic outcomes of immunotherapeutic interventions. Ythdf2 stabilized Cx3cl1 transcripts in an m⁶A-dependent manner, regulating the interplay between CD8⁺ T cells and the progression of liver malignancies. Thus, this study elucidated the novel role of hepatocyte YTHDF2, which promotes therapy-induced antitumor immune responses in the liver. The findings of this study provide valuable insights into the mechanism underlying the therapeutic benefits of targeting YTHDF2.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"23 1","pages":"186"},"PeriodicalIF":27.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}