journal
https://read.qxmd.com/read/38417668/circulating-tumor-cell-clustering-modulates-rna-splicing-and-polyadenylation-to-facilitate-metastasis
#1
JOURNAL ARTICLE
Quanyou Wu, Zhaoru Gu, Bingqing Shang, Duo Wan, Qi Zhang, Xiaoli Zhang, Peipei Xie, Shujun Cheng, Wen Zhang, Kaitai Zhang
Circulating tumor cell (CTC) clusters exhibit significantly higher metastatic potential compared to single CTCs. However, the underlying mechanism behind this phenomenon remains unclear, and the role of posttranscriptional RNA regulation in CTC clusters has not been explored. Here, we conducted a comparative analysis of alternative splicing (AS) and alternative polyadenylation (APA) profiles between single CTCs and CTC clusters. We identified 994 and 836 AS events in single CTCs and CTC clusters, respectively, with ∼20% of AS events showing differential regulation between the two cell types...
February 26, 2024: Cancer Letters
https://read.qxmd.com/read/38417667/exosomal-circrnas-novel-biomarkers-and-therapeutic-targets-for-urinary-tumors
#2
REVIEW
Qiang Liu, Shenglong Li
Exosomal circRNAs have emerged as promising biomarkers and therapeutic targets for urinary tumors. In this review, we explored the intricate role of exosomal circRNAs in urological cancers, focusing on their biological functions, dysregulation in tumors, and potential clinical applications. The review delves into the mechanisms by which exosomal circRNAs contribute to tumor progression and highlights their diagnostic and therapeutic implications. By synthesizing current research findings, we present a compelling case for the significance of exosomal circRNAs in the context of urinary tumors...
February 26, 2024: Cancer Letters
https://read.qxmd.com/read/38417666/tp53-in-mds-and-aml-biological-and-clinical-advances
#3
REVIEW
Yeqian Zhao, Weihao Chen, Jing Yu, Shanshan Pei, Qiang Zhang, Jimin Shi, He Huang, Yanmin Zhao
Recently, the WHO-5 and the ICC 2022 criteria have emphasized poor prognosis in AML/MDS patients with multi-hit TP53 mutations, whereas mutated TP53 plays a critical role in tumorigenesis, drawing substantial interest in exploring its biological behaviors. Diverse characteristics of TP53 mutations, including types, VAF, CNVs, allelic status, karyotypes, and concurrent mutations have been extensively studied. Novel potential targets and comprehensive treatment strategies nowadays are under swift development, owing to great advances in technology...
February 26, 2024: Cancer Letters
https://read.qxmd.com/read/38408604/lovastatin-sn38-co-loaded-liposomes-amplified-icb-therapeutic-effect-via-remodeling-the-immunologically-cold-colon-tumor-and-synergized-stimulation-of-cgas-sting-pathway
#4
JOURNAL ARTICLE
Yi Yang, Jialong Qi, Jialin Hu, You Zhou, Jiena Zheng, Wenxia Deng, Muhammad Inam, Jiaxin Guo, Yongyi Xie, Yuan Li, Chuanshan Xu, Wei Deng, Wenjie Chen
Current immune checkpoint blockade (ICB) immunotherapeutics have revolutionized cancer treatment. However, many cancers especially the "immunologically cold" tumors, do not respond to ICB, prompting the search for additional strategies to achieve durable responses. The cGAS-STING pathway, as an essential immune response pathway, has been demonstrated for a potent target to sensitize ICB immunotherapy. However, the low efficiency of conventional STING agonists limits their clinical application. Recent studies have shown that DNA topoisomerase I (TOPI) inhibitor chemodrug SN38 can activate the cGAS-STING pathway and induce an immune response through DNA damage, while the traditional statins medication lovastatin was found to inhibit DNA damage repair, which may in turn upregulate the damaged DNA level...
February 24, 2024: Cancer Letters
https://read.qxmd.com/read/38408603/potential-role-of-p53-deregulation-in-modulating-immune-responses-in-human-malignancies-a-paradigm-to-develop-immunotherapy
#5
JOURNAL ARTICLE
Shivi Chauhan, Shivani Jaiswal, Vibhuti Jakhmola, Bhavana Singh, Sujata Bhattacharya, Manoj Garg, Shinjinee Sengupta
The crucial role played by the oncogenic expression of TP53, stemming from mutation or amyloid formation, in various human malignancies has been extensively studied over the past two decades. Interestingly, the potential role of TP53 as a crucial player in modulating immune responses has provided new insight into the field of cancer biology. The loss of p53's transcriptional functions and/or the acquisition of tumorigenic properties can efficiently modulate the recruitment and functions of myeloid and lymphoid cells, ultimately leading to the evasion of immune responses in human tumors...
February 24, 2024: Cancer Letters
https://read.qxmd.com/read/38408602/sialyltransferase-st3gal4-confers-osimertinib-resistance-and-offers-strategies-to-overcome-resistance-in-non-small-cell-lung-cancer
#6
JOURNAL ARTICLE
Rui Han, Caiyu Lin, Conghua Lu, Yubo Wang, Jun Kang, Chen Hu, Yuanyao Dou, Di Wu, TingTing He, Huan Tang, Jie Zheng, Li Li, Yong He
The third-generation EGFR-TKI osimertinib is widely used in EGFR-mutated positive non-small cell lung cancer (NSCLC) patients, but drug resistance is inevitable. The currently known mechanisms only explain resistance in a small proportion of patients. For most patients, the mechanism of osimertinib resistance is still unclear, especially for EGFR-independent resistance. Herein, we thoroughly investigated the novel mechanism of osimertinib resistance and treatment strategies. We identified that ST3GAL4, a sialyltransferase, catalyzes terminal glycan sialylation of receptor protein tyrosine kinases, which induces acquired resistance to osimertinib in vitro and in vivo...
February 24, 2024: Cancer Letters
https://read.qxmd.com/read/38403110/cd63-cancer-associated-fibroblasts-confer-cdk4-6-inhibitor-resistance-to-breast-cancer-cells-by-exosomal-mir-20
#7
JOURNAL ARTICLE
Jiahui Sun, Ruoxin Du, Xiaoju Li, Chenlin Liu, Donghui Wang, Xiangmei He, Guodong Li, Kuo Zhang, Shuning Wang, Qiang Hao, Yingqi Zhang, Meng Li, Yuan Gao, Cun Zhang
Cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (CDK4/6i) have rapidly received Food and Drug Administration (FDA) approval as a new type of therapy for patients with advanced hormone receptor-positive breast cancer. However, with the widespread application of CDK4/6i, drug resistance has become a new challenge for clinical practice and has greatly limited the treatment effect. Here, the whole microenvironment landscape of ER+ breast cancer tumors was revealed through single-cell RNA sequencing, and a specific subset of cancer-associated fibroblasts (CD63+ CAFs) was identified as highly enriched in CDK4/6i resistant tumor tissues...
February 23, 2024: Cancer Letters
https://read.qxmd.com/read/38403109/clinical-sequencing-defines-the-somatic-and-germline-mutation-landscapes-of-chinese-her2-low-breast-cancer
#8
JOURNAL ARTICLE
Bo-Yue Han, Chao Chen, Hong Luo, Cai-Jin Lin, Xiang-Chen Han, Javaria Nasir, Jin-Xiu Shi, Wei Huang, Zhi-Ming Shao, Hong Ling, Xin Hu
More than half of the breast cancer initially labeled as human epidermal growth factor receptor 2 (HER2)-negative actually exhibited low HER2 levels (IHC 1+ or IHC 2+/FISH-) and were classified as HER2-low breast cancer. Previous research emphasized the significant biological heterogeneity in HER2-low breast cancer, highlighting the importance of accurately characterizing HER2-low tumors to promote the precise management of antibody‒drug conjugates. In this study, we established a large-scale targeted sequencing cohort (N = 1907) representing Chinese HER2-low breast cancer patients with detailed clinical annotation...
February 23, 2024: Cancer Letters
https://read.qxmd.com/read/38401888/pd-1-regulation-in-immune-homeostasis-and-immunotherapy
#9
REVIEW
Minling Gao, Jie Shi, Xiangling Xiao, Yingmeng Yao, Xu Chen, Bin Wang, Jinfang Zhang
Harnessing the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis is pivotal in autoimmunity and cancer immunotherapy. PD-1 receptors on immune cells engage with one of its ligands, PD-L1 or PD-L2, expressed on antigen-presenting cells or tumor cells, driving T-cell dysfunction and tumor immune escape. Thus, targeting PD-1/PD-L1 revitalizes cytotoxic T cells for cancer elimination. However, a majority of cancer patients don't respond to PD-1/PD-L1 blockade, and the underlying mechanisms remain partially understood...
February 22, 2024: Cancer Letters
https://read.qxmd.com/read/38401887/fundamental-insights-and-molecular-interactions-in-pancreatic-cancer-pathways-to-therapeutic-approaches
#10
JOURNAL ARTICLE
Ming Gu, Yang Liu, Peng Xin, Wei Guo, Zimo Zhao, Xu Yang, Ruiyang Ma, Taiwei Jiao, Wenhui Zheng
The gastrointestinal tract can be affected by a number of diseases that pancreatic cancer (PC) is a malignant manifestation of them. The prognosis of PC patients is unfavorable and because of their diagnosis at advanced stage, the treatment of this tumor is problematic. Owing to low survival rate, there is much interest towards understanding the molecular profile of PC in an attempt in developing more effective therapeutics. The conventional therapeutics for PC include surgery, chemotherapy and radiotherapy as well as emerging immunotherapy...
February 22, 2024: Cancer Letters
https://read.qxmd.com/read/38401886/linc02454-cct-complex-interaction-is-essential-for-telomerase-activity-and-cell-proliferation-in-head-and-neck-squamous-cell-carcinoma
#11
JOURNAL ARTICLE
Biying Chen, Yue Weng, Mingyue Li, Zhouliang Bian, Ye Tao, Wenkai Zhou, Hong Lu, Shufang He, Rijing Liao, Jie Huang, Qian Wang, Ming Xu, Yunhui Ge, Wei Cao, Ming Lei, Yanjie Zhang
Telomerase activity is upregulated in head and neck squamous cell carcinoma (HNSCC), yet its regulatory mechanisms remain unclear. Here, we identified a cancer-specific lncRNA (LINC02454) associated with poor prognosis by using LncRNA chip of our HNSCC cohorts and external datasets. Through employing negative-stain transmission electron microscopy (NS-TEM), we discovered an interaction between LINC02454 and CCT complex which would augment telomerase activity for maintaining telomere homeostasis. Supporting this, in the telomerase repeat amplification protocol (TRAP) assay and quantitative fluorescence in situ hybridization (Q-FISH) analysis, LINC02454 depletion significantly reduced telomerase activity and shortened telomere length...
February 22, 2024: Cancer Letters
https://read.qxmd.com/read/38401885/unleashing-the-power-of-immune-checkpoints-post-translational-modification-of-novel-molecules-and-clinical-applications
#12
REVIEW
Jie Wang, Yian Wang, Xianjie Jiang, Meifang Xu, Meifeng Wang, Rong Wang, Boshu Zheng, Mingfen Chen, Qi Ke, Jun Long
Immune checkpoint molecules play a pivotal role in the initiation, regulation, and termination of immune responses. Tumor cells exploit these checkpoints to dampen immune cell function, facilitating immune evasion. Clinical interventions target this mechanism by obstructing the binding of immune checkpoints to their ligands, thereby restoring the anti-tumor capabilities of immune cells. Notably, therapies centered on immune checkpoint inhibitors, particularly PD-1/PD-L1 and CTLA-4 blocking antibodies, have demonstrated significant clinical promise...
February 22, 2024: Cancer Letters
https://read.qxmd.com/read/38401884/targeting-o-glcnacylation-in-cancer-therapeutic-resistance-the-sugar-saga-continues
#13
REVIEW
Lulu Chen, Mengxue Hu, Luojun Chen, Yihan Peng, Cai Zhang, Xin Wang, Xiangpan Li, Yi Yao, Qibin Song, Jing Li, Huadong Pei
O-linked-N-acetylglucosaminylation (O-GlcNAcylation), a dynamic post-translational modification (PTM), holds profound implications in controlling various cellular processes such as cell signaling, metabolism, and epigenetic regulation that influence cancer progression and therapeutic resistance. From the therapeutic perspective, O-GlcNAc modulates drug efflux, targeting and metabolism. By integrating signals from glucose, lipid, amino acid, and nucleotide metabolic pathways, O-GlcNAc acts as a nutrient sensor and transmits signals to exerts its function on genome stability, epithelial-mesenchymal transition (EMT), cell stemness, cell apoptosis, autophagy, cell cycle...
February 22, 2024: Cancer Letters
https://read.qxmd.com/read/38395379/identification-of-a-9-gene-signature-to-enhance-biochemical-recurrence-prediction-in-primary-prostate-cancer-a-benchmarking-study-using-ten-machine-learning-methods-and-twelve-patient-cohorts
#14
JOURNAL ARTICLE
Wenjun Yin, Guo Chen, Yutong Li, Ruidong Li, Zhenyu Jia, Chuanfan Zhong, Shuo Wang, Xiangming Mao, Zhouda Cai, Junhong Deng, Weide Zhong, Bin Pan, Jianming Lu
Prostate cancer (PCa) is a prevalent malignancy among men worldwide, and biochemical recurrence (BCR) after radical prostatectomy (RP) is a critical turning point commonly used to guide the development of treatment strategies for primary PCa. However, the clinical parameters currently in use are inadequate for precise risk stratification and informing treatment choice. To address this issue, we conducted a study that collected transcriptomic data and clinical information from 1662 primary PCa patients across 12 multicenter cohorts globally...
February 21, 2024: Cancer Letters
https://read.qxmd.com/read/38395378/antigen-hla-agnostic-strategies-for-characterizing-tumor-responsive-t-cell-receptors-in-pdac-patients-via-single-cell-sequencing-and-autologous-organoid-application
#15
JOURNAL ARTICLE
Xu Wang, Zhengjie Dai, Xuan Lin, Xuan Zou, Ruijie Wang, Yesboli Tasiheng, Yu Yan, Mingjian Ma, Yusheng Chen, He Cheng, Chen Liu, Xianjun Yu
Characterization of tumor-responsive T cell receptors (TCRs) is a critical step in personalized TCR-T cell therapy, and remains challenging for pancreatic ductal adenocarcinoma (PDAC). Here we report a proof-of-concept study to identify and validate antitumor TCRs in two representative PDAC patients using ultradeep single-cell TCR/RNA sequencing and autologous organoids, and reveal the phenotypic dynamics of TCR repertoire in different T cell expansions from the same patient. We first performed comparative sequencing on freshly harvested peripheral blood mononuclear cells (PBMCs) and uncultured tumor infiltrating lymphocytes (TILs), followed by reactivity tests of TIL-enriched TCRs with autologous organoids, in which two tumor-responsive TCRs were successfully characterized and the corresponding TILs were mostly tissue-resident memory-like T cells, and partially expressed both naïve and exhausted T cell markers...
February 21, 2024: Cancer Letters
https://read.qxmd.com/read/38387757/revitalizing-antitumor-immunity-leveraging-nucleic-acid-sensors-as-therapeutic-targets
#16
REVIEW
Dan-Feng Liu, Wei He, Lei-Lei Yang
Nucleic acid sensors play a critical role in recognizing and responding to pathogenic nucleic acids as danger signals. Upon activation, these sensors initiate downstream signaling cascades that lead to the production and release of pro-inflammatory cytokines, chemokines, and type I interferons. These immune mediators orchestrate diverse effector responses, including the activation of immune cells and the modulation of the tumor microenvironment. However, careful consideration must be given to balancing the activation of nucleic acid sensors to avoid unwanted autoimmune or inflammatory responses...
February 20, 2024: Cancer Letters
https://read.qxmd.com/read/38387756/lnc-plcb1-is-stabilized-by-mettl14-induced-m6a-modification-and-inhibits-helicobacter-pylori-mediated-gastric-cancer-by-destabilizing-ddx21
#17
JOURNAL ARTICLE
Mingjie Chang, Qiyu Sun, Xixi Cui, Yuqiong Wang, Jiayi Liu, Zenghui Sun, Juchao Ren, Yundong Sun, Lihui Han, Wenjuan Li
Helicobacter pylori (H. pylori) infection is considered to be an important factor in gastric cancer (GC). Long noncoding RNA (lncRNA) and m6A modification are involved in the occurrence and development of GC, but the role of lncRNA m6A modification in the development of GC mediated by H. pylori is still unclear. Here, we found that H. pylori infection downregulated the expression of lnc-PLCB1 through METTL14-mediated m6A modification and IRF2-mediated transcriptional regulation. Overexpression of lnc-PLCB1 inhibited the proliferation and migration of GC cells, while downregulation of lnc-PLCB1 promoted the proliferation and migration ability of GC cells...
February 20, 2024: Cancer Letters
https://read.qxmd.com/read/38382667/a-growth-factor-reduced-culture-system-for-colorectal-cancer-organoids
#18
JOURNAL ARTICLE
Ronghui Tan, Ze Zhang, Peirong Ding, Yue Liu, Huidong Liu, Minyi Lu, Ye-Guang Chen
Although organoids derived from tumor tissues have been widely used in cancer research, it is a great challenge for cultured organoids to retain the characteristics of the original tumor tissues due to their heterogeneity. In this study, we explore organoid culture recipes to capture tumor features of colorectal cancers. We find that the activation of Wnt and EGF signaling and inhibition of BMP signaling are non-essential for the survival of most colorectal cancer organoids (CRCOs). We design a growth factor-reduced culture medium containing FGF10, A83-01 (TGF-β type I receptor inhibitor), SB202190 (p38 MAPK inhibitor), gastrin, and nicotinamide...
February 19, 2024: Cancer Letters
https://read.qxmd.com/read/38373691/cancer-resistance-and-metastasis-are-maintained-through-oxidative-phosphorylation
#19
REVIEW
Cemile Uslu, Eda Kapan, Alex Lyakhovich
Malignant tumors have increased energy requirements due to growth, differentiation or response to stress. A significant number of studies in recent years have described upregulation of mitochondrial genes responsible for oxidative phosphorylation (OXPHOS) in some tumors. Although OXPHOS is replaced by glycolysis in some tumors (Warburg effect), both processes can occur simultaneously during the evolution of the same malignancies. In particular, chemoresistant and/or cancer stem cells appear to find a way to activate OXPHOS and metastasize...
February 17, 2024: Cancer Letters
https://read.qxmd.com/read/38373690/sting-inhibitors-sensitize-platinum-chemotherapy-in-ovarian-cancer-by-inhibiting-the-cgas-sting-pathway-in-cancer-associated-fibroblasts-cafs
#20
JOURNAL ARTICLE
Jiale Liu, Chenmian Liu, Yana Ma, Xiyu Pan, Ran Chu, Shu Yao, Junyu Chen, Chang Liu, Zhongshao Chen, Chenchen Sheng, Kai Zhang, Ying Xue, Helgi B Schiƶth, Beihua Kong, Qing Zhang, Kun Song
Chemotherapy resistance in ovarian cancer hampers cure rates, with cancer-associated fibroblasts (CAFs) playing a pivotal role. Despite their known impact on cancer progression and chemotherapy resistance, the specific mechanism by which CAFs regulate the tumor inflammatory environment remains unclear. This study reveals that cisplatin facilitates DNA transfer from ovarian cancer cells to CAFs, activating the CGAS-STING-IFNB1 pathway in CAFs and promoting IFNB1 release. Consequently, this reinforces cancer cell resistance to platinum drugs...
February 17, 2024: Cancer Letters
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