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UBE2C mediates follicular thyroid carcinoma invasion and metastasis via K29-Specific vimentin ubiquitination UBE2C通过k29特异性波形蛋白泛素化介导滤泡性甲状腺癌的侵袭和转移。
IF 9.1 1区 医学
Cancer letters Pub Date : 2025-03-10 DOI: 10.1016/j.canlet.2025.217624
Lei Xu , Bao Dai , Lingyun Zhang , Weijian Chen , Shikuo Rong , Jianghong Chen , Muye Song , Ziteng Lan , Yongchen Liu , Linhe Wang , Jinghua Li , Jian Chen , Zeyu Wu
{"title":"UBE2C mediates follicular thyroid carcinoma invasion and metastasis via K29-Specific vimentin ubiquitination","authors":"Lei Xu ,&nbsp;Bao Dai ,&nbsp;Lingyun Zhang ,&nbsp;Weijian Chen ,&nbsp;Shikuo Rong ,&nbsp;Jianghong Chen ,&nbsp;Muye Song ,&nbsp;Ziteng Lan ,&nbsp;Yongchen Liu ,&nbsp;Linhe Wang ,&nbsp;Jinghua Li ,&nbsp;Jian Chen ,&nbsp;Zeyu Wu","doi":"10.1016/j.canlet.2025.217624","DOIUrl":"10.1016/j.canlet.2025.217624","url":null,"abstract":"<div><div>Follicular thyroid carcinoma (FTC) poses significant clinical challenges due to its vascular invasion tendency and distant metastasis potential, leading to poorer patient outcomes compared to other thyroid carcinomas. Although ubiquitin-conjugating enzyme E2C (UBE2C) has been widely studied in various cancers, its specific role in FTC progression remains insufficiently explored. This study demonstrates UBE2C's dual functionality in FTC through clinical analysis and experimental validation. Single-cell RNA sequencing of FTC specimens revealed marked UBE2C upregulation associated with aggressive tumor behavior and unfavorable prognosis. Functional studies showed that UBE2C overexpression paradoxically enhanced cellular proliferation while suppressing migration and invasion through EMT modulation. Mechanistic investigations identified vimentin as a key substrate, where UBE2C mediated K29-linked ubiquitination leading to its degradation. Animal models yielded unexpected findings where UBE2C knockdown reduced primary tumor growth but promoted metastasis, validating its context-dependent roles. These results establish UBE2C as a molecular regulator balancing proliferation and invasion in FTC through post-translational modification of cytoskeletal components, suggesting its therapeutic potential for targeted intervention strategies.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"617 ","pages":"Article 217624"},"PeriodicalIF":9.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613148","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
Innovative construction and application of bile duct organoids: Unraveling the complexity of bile duct diseases and potential therapeutic strategies 胆管类器官的创新构建和应用:揭示胆管疾病的复杂性和潜在的治疗策略。
IF 9.1 1区 医学
Cancer letters Pub Date : 2025-03-10 DOI: 10.1016/j.canlet.2025.217619
Yadi Geng , Ziye Chen , Tianzi Luo , Yakun Liu , Siming Kong , Xinlong Yan , Hui Bai , Yunfang Wang
{"title":"Innovative construction and application of bile duct organoids: Unraveling the complexity of bile duct diseases and potential therapeutic strategies","authors":"Yadi Geng ,&nbsp;Ziye Chen ,&nbsp;Tianzi Luo ,&nbsp;Yakun Liu ,&nbsp;Siming Kong ,&nbsp;Xinlong Yan ,&nbsp;Hui Bai ,&nbsp;Yunfang Wang","doi":"10.1016/j.canlet.2025.217619","DOIUrl":"10.1016/j.canlet.2025.217619","url":null,"abstract":"<div><div>The biliary system is crucial for liver function, regulating bile production, secretion, and transport. Dysfunctions within this system can lead to various diseases, such as cholangiopathies and biliary fibrosis, which may progress from benign to malignant states like cholangiocarcinoma. While liver organoid research is well-established and technologically advanced, bile duct organoids (BDOs) offer significant potential. BDOs can accurately simulate the physiological structure and function of bile ducts, making them valuable tools for <em>in-vitro</em> biliary disease research. Here, we review the development of BDO models, focusing on stem cell-derived organoids and tissue-derived organoids. We also illustrate the role of cultivation strategies and extracellular scaffolds in supporting organoid growth and stability, including the influence of cellular components of the microenvironment and physicochemical factors. Furthermore, we discuss the applications of BDOs in biliary development, disease modeling, regenerative medicine, and drug screening. Additionally, we emphasize the transformative potential in BDO biobanks and personalized medicine, which helps to pave the way for innovative therapeutic strategies and personalized medicine. Finally, we summarize the current and prospective advancements in BDO technologies, highlighting the integration of emerging technologies such as artificial intelligence, 3D bioprinting, and organoid-on-chip systems. These technologies hold great promise for significantly enhancing both clinical and research applications in the field of biliary diseases.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"618 ","pages":"Article 217619"},"PeriodicalIF":9.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613131","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
Enhanced mitochondrial biogenesis facilitates the development of cutaneous squamous cell carcinoma 线粒体生物发生的增强促进了皮肤鳞状细胞癌的发展。
IF 9.1 1区 医学
Cancer letters Pub Date : 2025-03-10 DOI: 10.1016/j.canlet.2025.217623
Ziyang Wang , Ke He , Meng Liu , Weiqiang Lv , Baochen Cheng , Guanfei Zhang , Xueqiang Wang , Mengqi Zeng , Lianying Jiao , Shujun Han , Yan Zheng , Zhihui Feng
{"title":"Enhanced mitochondrial biogenesis facilitates the development of cutaneous squamous cell carcinoma","authors":"Ziyang Wang ,&nbsp;Ke He ,&nbsp;Meng Liu ,&nbsp;Weiqiang Lv ,&nbsp;Baochen Cheng ,&nbsp;Guanfei Zhang ,&nbsp;Xueqiang Wang ,&nbsp;Mengqi Zeng ,&nbsp;Lianying Jiao ,&nbsp;Shujun Han ,&nbsp;Yan Zheng ,&nbsp;Zhihui Feng","doi":"10.1016/j.canlet.2025.217623","DOIUrl":"10.1016/j.canlet.2025.217623","url":null,"abstract":"<div><div>Mitochondrial malfunction is traditionally viewed as a major factor in tumor growth and malignancy, while recent studies have introduced conflicting views suggesting the necessity of functional mitochondria for tumor growth. Despite these differing perspectives, the specific role of mitochondria in cutaneous squamous cell carcinoma (cSCC) remains poorly understood. In this study, we observed increased mitochondrial abundance and function during the development of cSCC. We also identified retinoic acid receptor response 1 (RARRES1), which is dramatically decreased in human cSCC samples, as a key regulator of mitochondrial homeostasis. Mechanistically, RARRES1 can translocate into mitochondria and facilitate the degradation of TFAM by binding to LONP1, thereby regulating mitochondrial biogenesis. While RARRES1 suppression unleashed TFAM to promote mitochondrial biogenesis, leading to the progression of cSCC. Targeting RARRES1-LONP1/TFAM axis shows significant potential for inhibiting cSCC development. This study reveals a unique network for regulating mitochondrial homeostasis and emphasizes the crucial role of mitochondria in cSCC development, positioning the RARRES1-LONP1/TFAM axis as promising therapeutic target for future clinical applications.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"618 ","pages":"Article 217623"},"PeriodicalIF":9.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613129","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}
引用次数: 0
Irreversible electroporation combined with PD-L1/IL-6 dual blockade promotes anti-tumor immunity via cDC2/CD4+T cell axis in MHC-I deficient pancreatic cancer 不可逆电穿孔联合PD-L1/IL-6双阻断可通过cDC2/CD4+T细胞轴促进MHC-I缺陷胰腺癌的抗肿瘤免疫。
IF 9.1 1区 医学
Cancer letters Pub Date : 2025-03-09 DOI: 10.1016/j.canlet.2025.217620
Zhuozhuo Wu , Qungang Shan , Yuyue Jiang , Wei Huang , Ziyin Wang , Yaping Zhuang , Jingjing Liu , Tiankuan Li , Ziyu Yang , Chaojie Li , Tao Wei , Chenlei Wen , Wenguo Cui , Zilong Qiu , Xiaoyu Liu , Zhongmin Wang
{"title":"Irreversible electroporation combined with PD-L1/IL-6 dual blockade promotes anti-tumor immunity via cDC2/CD4+T cell axis in MHC-I deficient pancreatic cancer","authors":"Zhuozhuo Wu ,&nbsp;Qungang Shan ,&nbsp;Yuyue Jiang ,&nbsp;Wei Huang ,&nbsp;Ziyin Wang ,&nbsp;Yaping Zhuang ,&nbsp;Jingjing Liu ,&nbsp;Tiankuan Li ,&nbsp;Ziyu Yang ,&nbsp;Chaojie Li ,&nbsp;Tao Wei ,&nbsp;Chenlei Wen ,&nbsp;Wenguo Cui ,&nbsp;Zilong Qiu ,&nbsp;Xiaoyu Liu ,&nbsp;Zhongmin Wang","doi":"10.1016/j.canlet.2025.217620","DOIUrl":"10.1016/j.canlet.2025.217620","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is a “cold” solid tumor with frequent Major Histocompatibility Complex I (MHC-I) deficiency, thereby making it resistant to type-1-conventional dendritic cell (cDC1)-CD8<sup>+</sup>T cell mediated anti-tumor immunity. Current studies have demonstrated the emerging compensatory role of MHC-II-mediated antigen presentation and CD4<sup>+</sup>T cell activation in anti-tumor immunity against MHC-I-deficient tumors. However, the underlying mechanism of the compensatory immune response by CD4<sup>+</sup>T cells in cancer ablation therapy remains to be elucidate. In clinical samples and murine models, we observed that irreversible electroporation (IRE) ablation therapy promoted immune infiltration and the conversion of CD4<sup>+</sup>T cells into anti-tumor IFN-γ<sup>+</sup>Th1 cells and Th17 cells in MHC-I low-expressed PDAC using scRNA-seq and flow-cytometry analyses. Furthermore, we found that PD-L1 blockade predominantly enhanced the activation of CD11b<sup>+</sup>CD103<sup>-</sup>type-2 conventional dendritic cells (cDC2s) and their antigen presentation to CD4<sup>+</sup>T cells after ablation, stimulating the anti-tumor immune response through the tumor antigen-specific IFN-γ<sup>+</sup>Th1-NK cell axis. Elevated plasma levels of IL-6 in pancreatic cancer patients receiving ablation therapy are significant indicators for impaired prognosis. IL-6 and PD-L1 dual blockade could significantly augment the ratio of IFN-γ<sup>+</sup>Th1 in CD4<sup>+</sup>T cells to boost the anti-tumor immunity of NK cells, leading to prolonged survival of mouse bearing pancreatic cancer. Collectively, we have elucidated that PD-L1 blockade activates the cDC2-CD4<sup>+</sup>T cell axis after IRE therapy, thereby playing a pivotal compensatory anti-tumor role in MHC-I low-expressed pancreatic cancer. Moreover, a combination strategy involving dual-target blockade of PD-L1/IL-6 along with ablation therapy could emerge as a novel therapeutic approach for MHC-I deficient tumors.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"617 ","pages":"Article 217620"},"PeriodicalIF":9.1,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603974","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}
引用次数: 0
Osteopontin promotes tumor microenvironment remodeling and therapy resistance 骨桥蛋白促进肿瘤微环境重塑和治疗抵抗。
IF 9.1 1区 医学
Cancer letters Pub Date : 2025-03-08 DOI: 10.1016/j.canlet.2025.217618
Chao Liu , Shunjin Xia , Bo Wang , Jiayong Li , Xuyan Wang , Yu Ren , Xuan Zhou
{"title":"Osteopontin promotes tumor microenvironment remodeling and therapy resistance","authors":"Chao Liu ,&nbsp;Shunjin Xia ,&nbsp;Bo Wang ,&nbsp;Jiayong Li ,&nbsp;Xuyan Wang ,&nbsp;Yu Ren ,&nbsp;Xuan Zhou","doi":"10.1016/j.canlet.2025.217618","DOIUrl":"10.1016/j.canlet.2025.217618","url":null,"abstract":"<div><div>Osteopontin (OPN) is a multifunctional secretory protein which can be expressed and secreted by a variety of tumor cells and immune cells. Tumor microenvironment remodeling provides favorable conditions for tumor progression, immune escape and therapy resistance. As a bridge molecule in crosstalk between tumor cells and tumor microenvironment, OPN can not only come from tumor cells to regulate the functions of various immune cells, promoting the formation of immunosuppressive environment, but also can be secreted by immune cells to act on tumor cells, leading to tumor progression, thus constructing a positive feedback regulatory network. Here, we summarize the molecular structure, source and receptor of OPN, and clarify the mechanism of OPN on tumor-associated macrophages, dendritic cells, myeloid-derived suppressor cells, tumor progression and therapy resistance to comprehensively understand the great potential of OPN as a tumor biomarker and therapeutic target.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"617 ","pages":"Article 217618"},"PeriodicalIF":9.1,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584851","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
Clinical development of immuno-oncology therapeutics 免疫肿瘤学治疗的临床发展。
IF 9.1 1区 医学
Cancer letters Pub Date : 2025-03-06 DOI: 10.1016/j.canlet.2025.217616
Jianxin Wang , Qi Chen , qiang Shan , Tingbo Liang , Patrick Forde , Lei Zheng
{"title":"Clinical development of immuno-oncology therapeutics","authors":"Jianxin Wang ,&nbsp;Qi Chen ,&nbsp;qiang Shan ,&nbsp;Tingbo Liang ,&nbsp;Patrick Forde ,&nbsp;Lei Zheng","doi":"10.1016/j.canlet.2025.217616","DOIUrl":"10.1016/j.canlet.2025.217616","url":null,"abstract":"<div><div>Immuno-oncology (IO) is one of the fastest growing therapeutic areas within oncology. IO agents work indirectly via the host's adaptive and innate immune system to recognize and eradicate tumor cells. Despite checkpoint inhibitors being only introduced to the market since 2011, they have become the second most approved product category. Current Food and Drug Administration (FDA)-approved classes of IO agents include: immune checkpoint inhibitors (ICIs), chimeric antigen receptor T-cell therapy (CAR-T), bi-specific T-cell engager (BiTE) antibody therapy, T-cell receptor (TCR) engineered T cell therapy, tumor-infiltrating lymphocyte (TIL) therapy, cytokine therapy, cancer vaccine therapy, and oncolytic virus therapy. Cancer immunotherapy has made progress in multiple cancer types including melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), and urothelial carcinoma; however, several cancers remain refractory to immunotherapy. Future directions of IO include exploration in the neoadjuvant/perioperative setting, combination strategies, and optimizing patient selection through improved biomarkers.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"617 ","pages":"Article 217616"},"PeriodicalIF":9.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584849","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}
引用次数: 0
The carcinogenic metabolite acetaldehyde impairs cGAS activity to negatively regulate antiviral and antitumor immunity 致癌代谢物乙醛损害cGAS活性,负性调节抗病毒和抗肿瘤免疫。
IF 9.1 1区 医学
Cancer letters Pub Date : 2025-03-06 DOI: 10.1016/j.canlet.2025.217615
Xiao-Yue Zhou , Nian-Chao Zhang , Xia-Nan Zhang, Xue-Dan Sun, Zi-Lun Ruan, Qing Yang, Ming-Ming Hu, Hong-Bing Shu
{"title":"The carcinogenic metabolite acetaldehyde impairs cGAS activity to negatively regulate antiviral and antitumor immunity","authors":"Xiao-Yue Zhou ,&nbsp;Nian-Chao Zhang ,&nbsp;Xia-Nan Zhang,&nbsp;Xue-Dan Sun,&nbsp;Zi-Lun Ruan,&nbsp;Qing Yang,&nbsp;Ming-Ming Hu,&nbsp;Hong-Bing Shu","doi":"10.1016/j.canlet.2025.217615","DOIUrl":"10.1016/j.canlet.2025.217615","url":null,"abstract":"<div><div>The cGAS-MITA/STING pathway plays critical roles in both host defense against DNA virus and intrinsic antitumor immunity by sensing viral genomic DNA or dis-located mitochondrial/cellular DNA. Whether carcinogenic metabolites can target the cGAS-MITA axis to promote tumorigenesis is unknown. In this study, we identified acetaldehyde, a carcinogenic metabolite, as a suppressor of the cGAS-MITA pathway. Acetaldehyde inhibits the DNA virus herpes simplex virus 1 (HSV-1)- and transfected DNA-triggered but not cGAMP-induced activation of downstream components and induction of downstream effector genes. Mechanistically, acetaldehyde impairs the binding of cGAS to DNA as well as the phase separation of the cGAS-DNA complex in cells. In mouse models, acetaldehyde inhibits antiviral cytokine production, promotes viral replication and lethality upon HSV-1 infection. In a colorectal tumor xenograft model, acetaldehyde promotes tumor growth and inhibits CD8<sup>+</sup> T cell infiltration by targeting cGAS in both the tumor cells and immune cells in mice. Bioinformatic analysis indicates that expression of acetaldehyde dehydrogenase 2 (ALDH2), which converts acetaldehyde to acetic acid, is negatively correlated with stimulatory immune signatures in clinical colorectal tumors, and higher ALDH2 expression exhibits better prognosis of colorectal cancer patients. Collectively, our results suggest that acetaldehyde impairs cGAS activity to inhibit the cGAS-MITA axis, which contributes to its effects on carcinogenesis.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"617 ","pages":"Article 217615"},"PeriodicalIF":9.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584811","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
Corrigendum to “Protein profile in urinary extracellular vesicles is a marker of malignancy and correlates with muscle invasiveness in urinary bladder cancer” [Cancer Lett. 609 (2025) 217352] 尿细胞外囊泡蛋白是恶性肿瘤的标志物,与膀胱肿瘤的肌肉侵袭性相关[癌症杂志,609(2025)217352]。
IF 9.1 1区 医学
Cancer letters Pub Date : 2025-03-06 DOI: 10.1016/j.canlet.2025.217592
Loïc Steiner , Maria Eldh , Annemarijn Offens , Rosanne E. Veerman , Markus Johansson , Tammer Hemdan , Hans Netterling , Ylva Huge , Abdul-Sattar Aljabery Firas , Farhood Alamdari , Oskar Lidén , Amir Sherif , Susanne Gabrielsson
{"title":"Corrigendum to “Protein profile in urinary extracellular vesicles is a marker of malignancy and correlates with muscle invasiveness in urinary bladder cancer” [Cancer Lett. 609 (2025) 217352]","authors":"Loïc Steiner ,&nbsp;Maria Eldh ,&nbsp;Annemarijn Offens ,&nbsp;Rosanne E. Veerman ,&nbsp;Markus Johansson ,&nbsp;Tammer Hemdan ,&nbsp;Hans Netterling ,&nbsp;Ylva Huge ,&nbsp;Abdul-Sattar Aljabery Firas ,&nbsp;Farhood Alamdari ,&nbsp;Oskar Lidén ,&nbsp;Amir Sherif ,&nbsp;Susanne Gabrielsson","doi":"10.1016/j.canlet.2025.217592","DOIUrl":"10.1016/j.canlet.2025.217592","url":null,"abstract":"","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"616 ","pages":"Article 217592"},"PeriodicalIF":9.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572257","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}
引用次数: 0
SLC7A5/E2F1/PTBP1/PKM2 axis mediates progression and therapy effect of triple-negative breast cancer through the crosstalk of amino acid metabolism and glycolysis pathway SLC7A5/E2F1/PTBP1/PKM2轴通过氨基酸代谢和糖酵解途径的串扰介导三阴性乳腺癌的进展和治疗效果。
IF 9.1 1区 医学
Cancer letters Pub Date : 2025-03-05 DOI: 10.1016/j.canlet.2025.217612
Chengfei Jiang , Yingchen Qian , Xiaoming Bai , Shuangya Li , Liyuan Zhang , Yunxia Xie , Yifan Lu , Zhimin Lu , Bingjie Liu , Bing-Hua Jiang
{"title":"SLC7A5/E2F1/PTBP1/PKM2 axis mediates progression and therapy effect of triple-negative breast cancer through the crosstalk of amino acid metabolism and glycolysis pathway","authors":"Chengfei Jiang ,&nbsp;Yingchen Qian ,&nbsp;Xiaoming Bai ,&nbsp;Shuangya Li ,&nbsp;Liyuan Zhang ,&nbsp;Yunxia Xie ,&nbsp;Yifan Lu ,&nbsp;Zhimin Lu ,&nbsp;Bingjie Liu ,&nbsp;Bing-Hua Jiang","doi":"10.1016/j.canlet.2025.217612","DOIUrl":"10.1016/j.canlet.2025.217612","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) is one of the most challenging malignancies with the highest mortality rates among women. TNBC relies on both amino acid metabolism and glycolysis to fuel its bioenergetic and biosynthetic demands. However, the potential crosstalk between these two metabolic pathways and its impact on TNBC progression remain largely unexplored. In this study, we observed that SLC7A5, a key amino acid transporter, was upregulated in TNBC and strongly associated with poor patient prognosis. We demonstrated that the elevated SLC7A5 expression activated the amino acid pathway and promoted cell proliferation, tumor growth, and therapeutic resistance by inducing the switch from PKM1 to PKM2 expression, thereby mediating the crosstalk between amino acid metabolism and glycolysis. We further identified that the upregulation of SLC7A5 resulted from miR-152 suppression, which regulates TNBC cellular function and tumor growth. In addition, the miR-152/SLC7A5 axis mediated the expression of PTBP1, which maintains the balance between PKM1 and PKM2, linking amino acid signaling with the glycolysis pathway. To further understand the mechanism of PTBP1 upregulation, we identified that E2F1 transcriptionally activated PTBP1 expression through direct binding at the seed site, while E2F1 expression was also induced by SLC7A5 in TNBC. This novel SLC7A5/E2F1/PTBP1 axis plays a crucial role in regulating the crosstalk between amino acid signaling and glycolysis in TNBC and is essential for TNBC progression and therapeutic effectiveness. Our findings offer valuable insights into the molecular mechanisms underlying TNBC metabolic reprogramming and highlight potential targets for future therapeutic interventions.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"617 ","pages":"Article 217612"},"PeriodicalIF":9.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584852","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}
引用次数: 0
The landscape of malignant transition: Unraveling cancer cell-of-origin and heterogeneous tissue microenvironment 恶性转变的景观:解开癌细胞起源和异质组织微环境。
IF 9.1 1区 医学
Cancer letters Pub Date : 2025-03-05 DOI: 10.1016/j.canlet.2025.217591
Ruihan Luo , Jiajia Liu , Tiangang Wang , Weiling Zhao , Yanfei Wang , Jianguo Wen , Hongyu Wang , Shanli Ding , Xiaobo Zhou
{"title":"The landscape of malignant transition: Unraveling cancer cell-of-origin and heterogeneous tissue microenvironment","authors":"Ruihan Luo ,&nbsp;Jiajia Liu ,&nbsp;Tiangang Wang ,&nbsp;Weiling Zhao ,&nbsp;Yanfei Wang ,&nbsp;Jianguo Wen ,&nbsp;Hongyu Wang ,&nbsp;Shanli Ding ,&nbsp;Xiaobo Zhou","doi":"10.1016/j.canlet.2025.217591","DOIUrl":"10.1016/j.canlet.2025.217591","url":null,"abstract":"<div><div>Understanding disease progression and sophisticated tumor ecosystems is imperative for investigating tumorigenesis mechanisms and developing novel prevention strategies. Here, we dissected heterogeneous microenvironments during malignant transitions by leveraging data from 1396 samples spanning 13 major tissues. Within transitional stem-like subpopulations highly enriched in precancers and cancers, we identified 30 recurring cellular states strongly linked to malignancy, including hypoxia and epithelial senescence, revealing a high degree of plasticity in epithelial stem cells. By characterizing dynamics in stem-cell crosstalk with the microenvironment along the pseudotime axis, we found differential roles of ANXA1 at different stages of tumor development. In precancerous stages, reduced ANXA1 levels promoted monocyte differentiation toward M1 macrophages and inflammatory responses, whereas during malignant progression, upregulated ANXA1 fostered M2 macrophage polarization and cancer-associated fibroblast transformation by increasing TGF-β production. Our spatiotemporal analysis further provided insights into mechanisms responsible for immunosuppression and a potential target to control evolution of precancer and mitigate the risk for cancer development.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"621 ","pages":"Article 217591"},"PeriodicalIF":9.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584812","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
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