Cancer research最新文献_第5页

Adapt or Perish: Efficient Selenocysteine Insertion is Critical for Metastasizing Cancer Cells. 适应或灭亡：高效的硒半胱氨酸插入对转移癌细胞至关重要

IF 12.5 1区医学

Cancer research Pub Date : 2024-11-26 DOI: 10.1158/0008-5472.CAN-24-4442

Namgyu Lee, Dohoon Kim

引用次数: 0

Breast Cancer Subtype-Specific Organotropism is Dictated by FOXF2-Regulated Metastatic Dormancy and Recovery. 乳腺癌亚型特异性器官转移受 FOXF2 调节的转移蛰伏和恢复的支配

IF 12.5 1区医学

Cancer research Pub Date : 2024-11-26 DOI: 10.1158/0008-5472.CAN-24-0479

Wen-Jing Jiang, Tian-Hao Zhou, Huan-Jing Huang, Lin-Sen Li, Hao Tan, Rui Zhang, Qing-Shan Wang, Yu-Mei Feng

{"title":"Breast Cancer Subtype-Specific Organotropism is Dictated by FOXF2-Regulated Metastatic Dormancy and Recovery.","authors":"Wen-Jing Jiang, Tian-Hao Zhou, Huan-Jing Huang, Lin-Sen Li, Hao Tan, Rui Zhang, Qing-Shan Wang, Yu-Mei Feng","doi":"10.1158/0008-5472.CAN-24-0479","DOIUrl":"https://doi.org/10.1158/0008-5472.CAN-24-0479","url":null,"abstract":"Breast cancer subtypes display different metastatic organotropism. Identification of the mechanisms underlying subtype-specific organotropism could help uncover potential approaches to prevent and treat metastasis. Herein, we found that FOXF2 promoted the seeding and proliferative recovery from dormancy of luminal breast cancer (LumBC) and basal-like breast cancer (BLBC) cells in the bone by activating the NF-κB and BMP signaling pathways. Conversely, FOXF2 suppressed the seeding and proliferative recovery of BLBC cells in the lung by repressing the TGF-β signaling pathway. FOXF2 directly upregulated RelA/p65 transcription and expression in LumBC and BLBC cells by binding to the RELA proximal promoter region, and RelA/p65 bound to the FOXF2 proximal promoter region to upregulate expression, forming a positive feedback loop. Targeting the NF-κB pathway efficiently prevented the metastasis of FOXF2-overexpressing breast cancer cells to the bone, while inhibiting TGF-β signaling blocked the metastasis of BLBC with low FOXF2 expression to the lung. These findings uncover critical mechanisms of breast cancer subtype-specific organotropism and provide insight into precision assessment and treatment strategies.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715271","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

Stayin' Alive: Targeting chromatin regulators of clonal hematopoiesis promotes CD8 T cell stemness. 保持活着靶向克隆造血的染色质调节因子可促进 CD8 T 细胞的干性。

IF 12.5 1区医学

Cancer research Pub Date : 2024-11-26 DOI: 10.1158/0008-5472.CAN-24-4458

Xingjian Qiu, Aaron Yang, Amanda C Poholek

引用次数: 0

Fungal Influences on Cancer Initiation, Progression, and Response to Treatment. 真菌对癌症发生、发展和治疗反应的影响

IF 12.5 1区医学

Cancer research Pub Date : 2024-11-26 DOI: 10.1158/0008-5472.CAN-24-1609

Hazrat Bilal, Muhammad Nadeem Khan, Sabir Khan, Muhammad Shafiq, Wenjie Fang, Yuebin Zeng, Yangzhong Guo, Xiaohui Li, Bing Zhao, Qiao-Li Lv, Bin Xu

引用次数: 0

A Potent, Selective, Small-Molecule Inhibitor of DHX9 Abrogates Proliferation of Microsatellite Instable Cancers with Deficient Mismatch Repair. 一种强效、选择性小分子 DHX9 抑制剂可抑制错配修复缺陷的微卫星不稳定性癌症的增殖

IF 12.5 1区医学

Cancer research Pub Date : 2024-11-26 DOI: 10.1158/0008-5472.CAN-24-0397

Jennifer Castro, Matthew H Daniels, David Brennan, Brian Johnston, Deepali Gotur, Young-Tae Lee, Kevin E Knockenhauer, Chuang Lu, Jie Wu, Sunaina Nayak, Cindy Collins, Rishabh Bansal, Shane M Buker, April Case, Julie Liu, Shihua Yao, Brian A Sparling, E Allen Sickmier, Serena J Silver, Stephen J Blakemore, P Ann Boriack-Sjodin, Kenneth W Duncan, Scott Ribich, Robert A Copeland

{"title":"A Potent, Selective, Small-Molecule Inhibitor of DHX9 Abrogates Proliferation of Microsatellite Instable Cancers with Deficient Mismatch Repair.","authors":"Jennifer Castro, Matthew H Daniels, David Brennan, Brian Johnston, Deepali Gotur, Young-Tae Lee, Kevin E Knockenhauer, Chuang Lu, Jie Wu, Sunaina Nayak, Cindy Collins, Rishabh Bansal, Shane M Buker, April Case, Julie Liu, Shihua Yao, Brian A Sparling, E Allen Sickmier, Serena J Silver, Stephen J Blakemore, P Ann Boriack-Sjodin, Kenneth W Duncan, Scott Ribich, Robert A Copeland","doi":"10.1158/0008-5472.CAN-24-0397","DOIUrl":"https://doi.org/10.1158/0008-5472.CAN-24-0397","url":null,"abstract":"DHX9 is a multifunctional DExH-box RNA helicase with important roles in the regulation of transcription, translation, and maintenance of genome stability. Elevated expression of DHX9 is evident in multiple cancer types, including colorectal cancer (CRC). Microsatellite instable-high (MSI-H) tumors with deficient mismatch repair (dMMR) display a strong dependence on DHX9, making this helicase an attractive target for oncology drug discovery. In this report, we show that DHX9 knockdown increased RNA/DNA secondary structures and replication stress, resulting in cell cycle arrest and the onset of apoptosis in cancer cells with MSI-H/dMMR. ATX968 was identified as a potent and selective inhibitor of DHX9 helicase activity. Chemical inhibition of DHX9 enzymatic activity elicited similar selective effects on cell proliferation as seen with genetic knockdown. In addition, ATX968 induced robust and durable responses in an MSI-H/dMMR xenograft model but not in a microsatellite stable (MSS)/proficient mismatch repair (pMMR) model. These preclinical data validate DHX9 as a target for the treatment of patients with MSI-H/dMMR. Additionally, this potent and selective inhibitor of DHX9 provides a valuable tool with which to further explore the effects of inhibition of DHX9 enzymatic activity on the proliferation of cancer cells in vitro and in vivo.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715324","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

Mapping of the T Cell Landscape of Biliary Tract Cancer Unravels Anatomical Subtype-Specific Heterogeneity 胆道癌 T 细胞图谱揭示了解剖亚型特异性异质性

IF 11.2 1区医学

Cancer research Pub Date : 2024-11-21 DOI: 10.1158/0008-5472.can-24-1173

Jianhua Nie, Shuyuan Zhang, Ying Guo, Caiqi Liu, Jiaqi Shi, Haotian Wu, Ruisi Na, Yingjian Liang, Shan Yu, Fei Quan, Kun Liu, Mingwei Li, Meng Zhou, Ying Zhao, Xuehan Li, Shengnan Luo, Qian Zhang, Guangyu Wang, Yanqiao Zhang, Yuanfei Yao, Yun Xiao, Sheng Tai, Tongsen Zheng

{"title":"Mapping of the T Cell Landscape of Biliary Tract Cancer Unravels Anatomical Subtype-Specific Heterogeneity","authors":"Jianhua Nie, Shuyuan Zhang, Ying Guo, Caiqi Liu, Jiaqi Shi, Haotian Wu, Ruisi Na, Yingjian Liang, Shan Yu, Fei Quan, Kun Liu, Mingwei Li, Meng Zhou, Ying Zhao, Xuehan Li, Shengnan Luo, Qian Zhang, Guangyu Wang, Yanqiao Zhang, Yuanfei Yao, Yun Xiao, Sheng Tai, Tongsen Zheng","doi":"10.1158/0008-5472.can-24-1173","DOIUrl":"https://doi.org/10.1158/0008-5472.can-24-1173","url":null,"abstract":"Biliary tract cancer (BTC), encompassing diseases such as intrahepatic (ICC), extrahepatic cholangiocarcinoma (ECC), and gallbladder cancer (GBC), is not only on the rise but also poses a significant and urgent health threat due to its high malignancy. Genomic differences point to the possibility that these subtypes represent distinct diseases. Elucidation of the specific distribution of T cell subsets, critical to cancer immunity, across these diseases could provide better insights into the unique biology of BTC subtypes and help identify potential precision medicine strategies. To address this, we conducted scRNA-seq and scTCR-seq on CD3+ T cells from 36 samples from 16 BTC patients across all subtypes and analyzed 355 pathological slides to examine the spatial distribution of T cells and tertiary lymphoid structures (TLS). Compared to ICC and GBC, ECC possessed a unique immune profile characterized by T cell exhaustion, elevated CXCL13 expression in CD4+ T helper-like and CD8+CXCL13+ exhausted T cells, more mature TLS, and fewer desert immunophenotypes. Conversely, ICC displayed an inflamed immunophenotype with an enrichment of interferon related pathways and high expression of LGALS1 in activated regulatory T cells, associated with immunosuppression. Inhibition of LGALS1 reduced tumor growth and Treg prevalence in ICC mouse models. Overall, this study unveils T cell diversity across BTC subtypes at the single-cell and spatial level that could open paths for tailored immunotherapies.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"71 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684314","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

PTBP1 Lactylation Promotes Glioma Stem Cell Maintenance through PFKFB4-Driven Glycolysis PTBP1 乳化作用通过 PFKFB4 驱动的糖酵解促进胶质瘤干细胞的维持

IF 11.2 1区医学

Cancer research Pub Date : 2024-11-21 DOI: 10.1158/0008-5472.can-24-1412

Zijian Zhou, Xianyong Yin, Hao Sun, Jiaze Lu, Yuming Li, Yang Fan, Peiwen Lv, Min Han, Jing Wu, Shengjie Li, Zihao Liu, Hongbo Zhao, Haohan Sun, Hao Fan, Shan Wang, Tao Xin

{"title":"PTBP1 Lactylation Promotes Glioma Stem Cell Maintenance through PFKFB4-Driven Glycolysis","authors":"Zijian Zhou, Xianyong Yin, Hao Sun, Jiaze Lu, Yuming Li, Yang Fan, Peiwen Lv, Min Han, Jing Wu, Shengjie Li, Zihao Liu, Hongbo Zhao, Haohan Sun, Hao Fan, Shan Wang, Tao Xin","doi":"10.1158/0008-5472.can-24-1412","DOIUrl":"https://doi.org/10.1158/0008-5472.can-24-1412","url":null,"abstract":"Longstanding evidence implicates glioma stem cells (GSCs) as the major driver for glioma propagation and recurrence. GSCs have a distinctive metabolic landscape characterized by elevated glycolysis. Lactate accumulation resulting from enhanced glycolytic activity can drive lysine lactylation to regulate protein functions, suggesting that elucidating the lactylation landscape in GSCs could provide insights into glioma biology. Herein, we demonstrated that global lactylation was significantly elevated in GSCs compared to differentiated glioma cells (DGCs). PTBP1, a central regulator of RNA processing, was hyperlactylated in GSCs, and SIRT1 induced PTBP1 delactylation. PTBP1-K436 lactylation supported glioma progression and GSC maintenance. Mechanistically, K436 lactylation inhibited PTBP1 proteasomal degradation by attenuating the interaction with TRIM21. Moreover, PTBP1 lactylation enhanced its RNA-binding capacity and facilitated PFKFB4 mRNA stabilization, which further increased glycolysis. Together, these findings uncovered a lactylation-mediated mechanism in GSCs driven by metabolic reprogramming that induces aberrant epigenetic modifications to further stimulate glycolysis, resulting in a vicious cycle to exacerbate tumorigenesis.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"15 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684318","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

IF 11.2 1区医学

Cancer research Pub Date : 2024-11-21 DOI: 10.1158/0008-5472.can-24-3041

Sylvia L. Crowder, Lisa M. Gudenkauf, Aasha I. Hoogland, Hyo S. Han, Brent J. Small, Tiffany L. Carson, Nathan H. Parker, Margaret Booth-Jones, Heather S.L. Jim

{"title":"Cancer-Related Cognitive Impairment and the Potential of Dietary Interventions for the Prevention and Mitigation of Neurodegeneration","authors":"Sylvia L. Crowder, Lisa M. Gudenkauf, Aasha I. Hoogland, Hyo S. Han, Brent J. Small, Tiffany L. Carson, Nathan H. Parker, Margaret Booth-Jones, Heather S.L. Jim","doi":"10.1158/0008-5472.can-24-3041","DOIUrl":"https://doi.org/10.1158/0008-5472.can-24-3041","url":null,"abstract":"Approximately 35% of long-term cancer survivors experience ongoing cancer-related cognitive impairment (CRCI). Yet, few efficacious interventions exist to prevent or ameliorate CRCI. The underlying biological processes driving CRCI are complex and are reported to include changes in brain structure and function, increased oxidative stress and inflammation, and alterations in gut microbiome composition. Some of the mechanisms promoting CRCI have the potential to be modified through behavioral changes, such as dietary changes. Compelling evidence from randomized controlled trials and observational research supports the positive impacts of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet on cognition outside of the context of cancer, but studies investigating the MIND diet as an intervention for people who experience CRCI are lacking. This review examines the current state of the science for cognitive outcomes of dietary interventions in aging populations and discusses future opportunities to adapt these interventions to cancer populations.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"46 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684279","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

Midkine at the Crossroads of Aging and Cancer 处于衰老与癌症交叉口的 Midkine

IF 11.2 1区医学

Cancer research Pub Date : 2024-11-21 DOI: 10.1158/0008-5472.can-24-4381

Huiru Bai, Shang Cai

引用次数: 0

Multi-omics Analysis Reveals Molecular Changes During Early Progression of Precancerous Lesions to Lung Adenocarcinoma in Never-Smokers 多组学分析揭示了从不吸烟者肺癌前病变向肺腺癌早期进展过程中的分子变化

IF 11.2 1区医学

Cancer research Pub Date : 2024-11-21 DOI: 10.1158/0008-5472.can-24-0821

Yun-Ching Chen, Chia-Lang Hsu, Hui-Min Wang, Shang-Gin Wu, Yih-Leong Chang, Jin-Shing Chen, Yu-Ching Wu, Yen-Ting Lin, Ching-Yao Yang, Mong-Wei Lin, Jang-Ming Lee, Shuenn-Wen Kuo, Ke-Cheng Chen, Hsao-Hsun Hsu, Pei-Ming Huang, Yen-Lin Huang, Chong-Jen Yu, Mehdi Pirooznia, Bevan E. Huang, Rob Yang, Jin-Yuan Shih, Pan-Chyr Yang

{"title":"Multi-omics Analysis Reveals Molecular Changes During Early Progression of Precancerous Lesions to Lung Adenocarcinoma in Never-Smokers","authors":"Yun-Ching Chen, Chia-Lang Hsu, Hui-Min Wang, Shang-Gin Wu, Yih-Leong Chang, Jin-Shing Chen, Yu-Ching Wu, Yen-Ting Lin, Ching-Yao Yang, Mong-Wei Lin, Jang-Ming Lee, Shuenn-Wen Kuo, Ke-Cheng Chen, Hsao-Hsun Hsu, Pei-Ming Huang, Yen-Lin Huang, Chong-Jen Yu, Mehdi Pirooznia, Bevan E. Huang, Rob Yang, Jin-Yuan Shih, Pan-Chyr Yang","doi":"10.1158/0008-5472.can-24-0821","DOIUrl":"https://doi.org/10.1158/0008-5472.can-24-0821","url":null,"abstract":"Lung cancer is the most common cause of cancer mortality globally, and the prevalence of lung adenocarcinoma (LUAD), the most common lung cancer subtype, has increased sharply in East Asia. Early diagnosis leads to better survival rates, but this requires an improved understanding of the molecular changes during early tumorigenesis, particularly in non-smokers. Here, we performed whole exome-sequencing and RNA-sequencing of samples from 94 East Asian patients with precancerous lesions (25 with atypical adenomatous hyperplasia [AAH]; 69 with adenocarcinoma in situ [AIS]) and 73 patients with early invasive lesions (minimally invasive adenocarcinoma [MIA]). Cellular analysis revealed that the activities of endothelial and stromal cells could be used to categorize tumors into molecular subtypes within pathologically defined types of lesions. The subtypes were linked with the radiologically defined type of lesions and corresponded to immune cell infiltration throughout the early progression of LUAD. Spatial transcriptomic analysis revealed the distribution of epithelial cells, endothelial cells, fibroblasts, and plasma cells within MIA samples. Characterization of the molecular lesion subtypes identified positively selected mutational patterns and suggested that angiogenesis in the late-stage AIS type potentially contributes to tissue invasion of the MIA type. This study offers a resource that may help to improve early diagnosis and patient prognosis, and the findings suggest possible approaches for early disease interception.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":"11 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684275","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