Cancer letters最新文献_第10页

The eIF3a translational control axis in the Wnt/β-catenin signaling pathway and colon tumorigenesis Wnt/β-catenin信号通路中的eIF3a翻译控制轴与结肠肿瘤发生。

IF 9.1 1区医学

Cancer letters Pub Date : 2024-10-15 DOI: 10.1016/j.canlet.2024.217303

Zizheng Dong, Anuj Ojha, Lincoln Barlow, Liyun Luo, Jing-Yuan Liu, Jian-Ting Zhang

{"title":"The eIF3a translational control axis in the Wnt/β-catenin signaling pathway and colon tumorigenesis","authors":"Zizheng Dong, Anuj Ojha, Lincoln Barlow, Liyun Luo, Jing-Yuan Liu, Jian-Ting Zhang","doi":"10.1016/j.canlet.2024.217303","DOIUrl":"10.1016/j.canlet.2024.217303","url":null,"abstract":"<div><div>Translational initiation in protein synthesis is an important regulatory step in gene expression and its dysregulation may result in diseases such as cancer. Translational control by eIF4E/4<em>E</em>-BP has been well studied and contributes to mTOR signaling in various biological processes. Here, we report a novel translational control axis in the Wnt/β-catenin signaling pathway in colon tumorigenesis by eIF3a, a Yin-Yang factor in tumorigenesis and prognosis. We show that eIF3a expression is upregulated in human colon cancer tissues, pre-cancerous adenoma polyps, and associates with β-catenin level and APC mutation in human samples, and that eIF3a overexpression transforms intestinal epithelial cells. We also show that eIF3a expression is regulated by the Wnt/β-catenin signaling pathway with an active TCF/LEF binding site in its promoter and that eIF3a knockdown inhibits APC mutation-induced spontaneous colon tumorigenesis in APC<sup>min/+</sup> mice. Together, we conclude that eIF3a upregulation in colon cancer is due to APC mutation and it participates in colon tumorigenesis by adding a translational control axis in the Wnt/β-catenin signaling pathway and that it can serve as a potential target for colon cancer intervention.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"605 ","pages":"Article 217303"},"PeriodicalIF":9.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458634","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

Evaluation of glucocorticoid-related genes reveals GPD1 as a therapeutic target and regulator of sphingosine 1-phosphate metabolism in CRPC 对糖皮质激素相关基因的评估显示 GPD1 是 CRPC 的治疗靶点和 1-磷酸鞘磷脂代谢的调节器。

IF 9.1 1区医学

Cancer letters Pub Date : 2024-10-15 DOI: 10.1016/j.canlet.2024.217286

Ren Liu , Zhihao Zou , Zhengrong Zhang , Huichan He , Ming Xi , Yingke Liang , Jianheng Ye , Qishan Dai , Yongding Wu , Huijing Tan , Weide Zhong , Zongren Wang , Yuxiang Liang

{"title":"Evaluation of glucocorticoid-related genes reveals GPD1 as a therapeutic target and regulator of sphingosine 1-phosphate metabolism in CRPC","authors":"Ren Liu , Zhihao Zou , Zhengrong Zhang , Huichan He , Ming Xi , Yingke Liang , Jianheng Ye , Qishan Dai , Yongding Wu , Huijing Tan , Weide Zhong , Zongren Wang , Yuxiang Liang","doi":"10.1016/j.canlet.2024.217286","DOIUrl":"10.1016/j.canlet.2024.217286","url":null,"abstract":"<div><div>Prostate cancer (PCa) is an androgen-dependent disease, with castration-resistant prostate cancer (CRPC) being an advanced stage that no longer responds to androgen deprivation therapy (ADT). Mounting evidence suggests that glucocorticoid receptors (GR) confer resistance to ADT in CRPC patients by bypassing androgen receptor (AR) blockade. GR, as a novel therapeutic target in CRPC, has attracted substantial attention worldwide. This study utilized bioinformatic analysis of publicly available CRPC single-cell data to develop a consensus glucocorticoid-related signature (Glu-sig) that can serve as an independent predictor for relapse-free survival. Our results revealed that the signature demonstrated consistent and robust performance across seven publicly accessible datasets and an internal cohort. Furthermore, our findings demonstrated that glycerol-3-phosphate dehydrogenase 1 (GPD1) in Glu-sig can significantly promote CRPC progression by mediating the cell cycle pathway. Additionally, GPD1 was shown to be regulated by GR, with the GR antagonist mifepristone enhancing the anti-tumorigenic effects of GPD1 in CRPC cells. Mechanistically, targeting GPD1 induced the production of sphingosine 1-phosphate (S1P) and enhanced histone acetylation, thereby inducing the transcription of p21 that involved in cell cycle regulation. In conclusion, Glu-sig could serve as a robust and promising tool to improve the clinical outcomes of PCa patients, and modulating the GR/GPD1 axis that promotes tumor growth may be a promising approach for delaying CRPC progression.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"605 ","pages":"Article 217286"},"PeriodicalIF":9.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458719","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

Inhibition of TGF-β signaling in bone marrow endothelial cells promotes hematopoietic recovery in acute myeloid leukemia patients 抑制骨髓内皮细胞中的 TGF-β 信号传导可促进急性髓性白血病患者的造血功能恢复。

IF 9.1 1区医学

Cancer letters Pub Date : 2024-10-11 DOI: 10.1016/j.canlet.2024.217290

Zhen-Kun Wang , Zhi-Wei Zhang , Zhong-Shi Lyu , Tong Xing , Mi Liang , Meng-Zhu Shen , Chen-Yuan Li , Xin-Yan Zhang , Dan-Dan Chen , Ya-Zhe Wang , Li-Juan Hu , Hao Jiang , Yu Wang , Qian Jiang , Xiao-Hui Zhang , Yuan Kong , Xiao-Jun Huang

{"title":"Inhibition of TGF-β signaling in bone marrow endothelial cells promotes hematopoietic recovery in acute myeloid leukemia patients","authors":"Zhen-Kun Wang , Zhi-Wei Zhang , Zhong-Shi Lyu , Tong Xing , Mi Liang , Meng-Zhu Shen , Chen-Yuan Li , Xin-Yan Zhang , Dan-Dan Chen , Ya-Zhe Wang , Li-Juan Hu , Hao Jiang , Yu Wang , Qian Jiang , Xiao-Hui Zhang , Yuan Kong , Xiao-Jun Huang","doi":"10.1016/j.canlet.2024.217290","DOIUrl":"10.1016/j.canlet.2024.217290","url":null,"abstract":"<div><div>Although it is an effective treatment for acute myeloid leukemia (AML), chemotherapy leads to myelosuppression and poor hematopoietic reconstruction. Hematopoiesis is regulated by bone marrow (BM) endothelial cells (ECs), and BM ECs are dysfunctional in acute leukemia patients with poor hematopoietic reconstitution after allogenic hematopoietic stem cell transplantation. Thus, it is crucial to explore the underlying mechanism of EC impairment and establish strategies for targeted therapy. TGF-β signaling was found to be upregulated in ECs from AML patients in complete remission (CR ECs) and led to CR EC damage. Administration of a TGF-β inhibitor rescued the dysfunction of ECs caused by TGF-β1 expression <em>in vitro</em>, especially their hematopoiesis-supporting ability. Moreover, inhibition of TGF-β expression repaired the BM EC damage triggered by chemotherapy in both AML patients <em>in vitro</em> and in an AML-CR murine model, and restored normal hematopoiesis without promoting AML progression. Mechanistically, our data reveal alterations in the transcriptomic pattern of damaged BM ECs, accompanied by the overexpression of downstream molecules TGF-βR1, pSmad2/3, and functional genes related to adhesion, angiogenesis suppression and pro-apoptosis. Collectively, our findings reveal for the first time that the activation of TGF-β signaling leads to BM EC dysfunction and poor hematopoietic reconstitution. Targeting TGF-β represents a potential therapeutic strategy to promote multilineage hematopoiesis, thereby benefiting more cancer patients who suffer from myelosuppression after chemotherapy.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"605 ","pages":"Article 217290"},"PeriodicalIF":9.1,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458633","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

Autophagy and cancer therapy 自噬与癌症治疗

IF 9.1 1区医学

Cancer letters Pub Date : 2024-10-10 DOI: 10.1016/j.canlet.2024.217285

Julio M. Pimentel , Jun Ying Zhou , Gen Sheng Wu

引用次数: 0

S100A7 orchestrates neutrophil chemotaxis and drives neutrophil extracellular traps (NETs) formation to facilitate lymph node metastasis in cervical cancer patients S100A7 可协调中性粒细胞趋化并推动中性粒细胞胞外捕获物 (NET) 的形成，从而促进宫颈癌患者的淋巴结转移。

IF 9.1 1区医学

Cancer letters Pub Date : 2024-10-09 DOI: 10.1016/j.canlet.2024.217288

Ying Ning , Yu Chen , Tian Tian , Xinyan Gao , Xiaolan Liu , Jia Wang , Huijun Chu , Chenyang Zhao , Yufei Yang , Ke Lei , He Ren , Zhumei Cui

{"title":"S100A7 orchestrates neutrophil chemotaxis and drives neutrophil extracellular traps (NETs) formation to facilitate lymph node metastasis in cervical cancer patients","authors":"Ying Ning , Yu Chen , Tian Tian , Xinyan Gao , Xiaolan Liu , Jia Wang , Huijun Chu , Chenyang Zhao , Yufei Yang , Ke Lei , He Ren , Zhumei Cui","doi":"10.1016/j.canlet.2024.217288","DOIUrl":"10.1016/j.canlet.2024.217288","url":null,"abstract":"<div><div>Neutrophil extracellular traps (NETs) have been shown to promote the metastatic potential of many kinds of tumors. Our study aimed to investigate the role and mechanisms of NETs in lymph node metastasis (LNM) of cervical cancer (CCa), and evaluated the therapeutic value of targeting NETs in CCa. Immunohistochemistry demonstrated that neutrophil infiltration and NETs formation were increased in CCa patients with LNM, as well as confirming a positive correlation between S100A7 expression and neutrophil infiltration in CCa. NETs enhanced the migratory capability of CCa by activating the P38-MAPK/ERK/NFκB pathway through interaction with TLR2. Digesting NETs with deoxyribonuclease 1 (DNase 1) or inhibiting TLR2 with chloroquine eliminated the NETs-induced metastatic potential of CCa. Additionally, NETs promoted lymphangiogenesis and increased the permeability of lymphatic vessels, thus facilitating translymphatic movement of CCa. CCa-derived S100A7 exhibited a chemotactic effect on neutrophils and promoted NETs generation by elevating ROS levels rather than activating autophagy in neutrophils. The mouse model with footpad implantation illustrated that DNase 1 effectively reduced LNM in LPS-induced mice and in mice seeded with S100A7-overexpressing CCa cells. In conclusion, our study reveals a new tumor-promoting mechanism of S100A7, clarifies the crucial role and mechanism of NETs in LNM of CCa, and indicates that the NETs-targeted therapy emerges as a promising anti-metastasis therapy in CCa.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"605 ","pages":"Article 217288"},"PeriodicalIF":9.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388323","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

Pirfenidone antagonizes TGF-β1-mediated gabapentin resistance via reversal of desmoplasia and the ‘cold’ microenvironment in pancreatic cancer 吡非尼酮通过逆转胰腺癌的脱落细胞和 "冷 "微环境拮抗TGF-β1介导的加巴喷丁抗性

IF 9.1 1区医学

Cancer letters Pub Date : 2024-10-09 DOI: 10.1016/j.canlet.2024.217287

Jin Zhang , Junrong Zhang , Ronggui Lin , Ping Hou , Lihong Zheng , Chenwei Jiang , Da Zhang , Heguang Huang , Tianhong Teng

{"title":"Pirfenidone antagonizes TGF-β1-mediated gabapentin resistance via reversal of desmoplasia and the ‘cold’ microenvironment in pancreatic cancer","authors":"Jin Zhang , Junrong Zhang , Ronggui Lin , Ping Hou , Lihong Zheng , Chenwei Jiang , Da Zhang , Heguang Huang , Tianhong Teng","doi":"10.1016/j.canlet.2024.217287","DOIUrl":"10.1016/j.canlet.2024.217287","url":null,"abstract":"<div><div>Owing to the desmoplastic stroma constituted by cancer-associated fibroblasts (CAFs), few immune cells infiltrate the pancreatic ductal adenocarcinoma (PDAC). Gabapentin can impede the production of ketoacids by CAFs to support cancer cells. However, in our study, we discovered a dose-dependent increase in transforming growth factor β1 (TGF-β1) levels in cancer cells in response to gabapentin. This reverse increase of TGF-β1 contributes to 'Gabapentin-resistance', leading to the antitumor effects on PDAC cell lines are negatively negotiated in the presence of pancreatic stellate cells. Pirfenidone synergistically inhibited the growth and apoptosis resistance of PDAC when combined with Gabapentin. In a mouse orthotopic PDAC model, Fe<sup>3+</sup>-mediated coordination nanodrugs, which contain gabapentin, pirfenidone and the natural polyphenol (EGCG), efficiently promoted the infiltration of naïve CD8<sup>+</sup> T cells (CD44<sup>low</sup>CD62L<sup>high</sup>) and the accumulation of inflammatory CAFs (α-SMA<sup>low</sup>IL-6<sup>high</sup>). This led to a nearly two-fold increase in survival compared to the control. Furthermore, we identified a new subpopulation as Hmox1<sup>high</sup>iCAFs following treatment with our nanodrugs. Hmox1<sup>high</sup>iCAFs overexpressed the Cxcl10 receptor (Sdc4) and facilitated functional CD8<sup>+</sup> T-cell infiltration through the Tnfsf9-Tnfrsf9 axis. Overall, our nanodrugs reshape the phenotype of CAFs and enhance functional CD8<sup>+</sup> T-cell infiltration into tumors, holding the potential to be a safe and promising therapy for PDAC.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"605 ","pages":"Article 217287"},"PeriodicalIF":9.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399496","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

Pancreatic cancer cell-derived migrasomes promote cancer progression by fostering an immunosuppressive tumor microenvironment 胰腺癌细胞衍生的移行体通过培养免疫抑制性肿瘤微环境促进癌症进展

IF 9.1 1区医学

Cancer letters Pub Date : 2024-10-09 DOI: 10.1016/j.canlet.2024.217289

Ronghua Zhang , Junya Peng , Yalu Zhang , Kexin Zheng , Yang Chen , Lulu Liu , Tong Li , Jingkai Liu , Ying Li , Sen Yang , Mengyi Wang , Ming Cui , Xiang Zhang , Junyi Gao , Jorg Kleeff , Quan Liao , Qiaofei Liu

{"title":"Pancreatic cancer cell-derived migrasomes promote cancer progression by fostering an immunosuppressive tumor microenvironment","authors":"Ronghua Zhang , Junya Peng , Yalu Zhang , Kexin Zheng , Yang Chen , Lulu Liu , Tong Li , Jingkai Liu , Ying Li , Sen Yang , Mengyi Wang , Ming Cui , Xiang Zhang , Junyi Gao , Jorg Kleeff , Quan Liao , Qiaofei Liu","doi":"10.1016/j.canlet.2024.217289","DOIUrl":"10.1016/j.canlet.2024.217289","url":null,"abstract":"<div><div>Pancreatic cancer is distinguished by an immunosuppressive tumor microenvironment (TME) that facilitates cancer progression. The assembly of the TME involves numerous contributing factors. Migrasomes, recently identified as cellular organelles in migrating cells, play a pivotal role in intercellular signaling. However, research into their involvement in cancers remains nascent. Thus far, whether pancreatic cancer cells generate migrasomes and their potential role in TME formation remains unexplored. In this study, it was found that both murine and human pancreatic cancer cells could indeed generate migrasomes, termed pancreatic cancer cell-derived migrasomes (PCDMs), which actively promote cancer progression. Moreover, utilizing chemokine antibody arrays and quantitative mass spectrometry analysis, we observed significant differences between the chemokines, cytokines, and proteins present in PCDMs compared to their originating cell bodies. Notably, PCDMs exhibited an enrichment of immunosuppression-inducing factors. Furthermore, macrophages could directly uptake PCDMs, leading to the expression of high levels of M2-like markers and secretion of tumor-promoting factors. PCDM-induced macrophages played a pivotal role in inhibiting T cell proliferation and activation partially through ARG-1. In summary, this study provides compelling evidence that pancreatic cancer cells generate migrasomes, which play a crucial role in promoting tumor progression by contributing to an immunosuppressive TME. The exploration of migrasomes as a therapeutic target could pave the way for the development of tailored immunotherapies for pancreatic cancer.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"605 ","pages":"Article 217289"},"PeriodicalIF":9.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399495","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

Therapeutic potential of tumor-infiltrating lymphocytes in non-small cell lung cancer 肿瘤浸润淋巴细胞在非小细胞肺癌中的治疗潜力。

IF 9.1 1区医学

Cancer letters Pub Date : 2024-10-05 DOI: 10.1016/j.canlet.2024.217281

Daniel R. Plaugher , Avery R. Childress , Christian M. Gosser , Dave-Preston Esoe , Kassandra J. Naughton , Zhonglin Hao , Christine F. Brainson

{"title":"Therapeutic potential of tumor-infiltrating lymphocytes in non-small cell lung cancer","authors":"Daniel R. Plaugher , Avery R. Childress , Christian M. Gosser , Dave-Preston Esoe , Kassandra J. Naughton , Zhonglin Hao , Christine F. Brainson","doi":"10.1016/j.canlet.2024.217281","DOIUrl":"10.1016/j.canlet.2024.217281","url":null,"abstract":"<div><div>Lung cancer is the leading cause of cancer-related death worldwide, with poor outcomes even for those diagnosed at early stages. Current standard-of-care for most non-small cell lung cancer (NSCLC) patients involves an array of chemotherapy, radiotherapy, immunotherapy, targeted therapy, and surgical resection depending on the stage and location of the cancer. While patient outcomes have certainly improved, advances in highly personalized care remain limited. However, there is growing excitement around harnessing the power of tumor-infiltrating lymphocytes (TILs) through the use of adoptive cell transfer (ACT) therapy. These TILs are naturally occurring, may already recognize tumor-specific antigens, and can have direct anti-cancer effect. In this review, we highlight comparisons of various ACTs, including a brief TIL history, show current advances and successes of TIL therapy in NSCLC, discuss the potential roles for epigenetics in T cell expansion, and highlight challenges and future directions of the field to combat NSCLC in a personalized manner.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"605 ","pages":"Article 217281"},"PeriodicalIF":9.1,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380097","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

SMARCA4 and SMARCA2 co-deficiency: An uncommon molecular signature defining a subset of rare, aggressive and undifferentiated malignancies associated with defective chromatin remodeling SMARCA4和SMARCA2共同缺陷：一种不常见的分子特征，可定义与染色质重塑缺陷有关的罕见、侵袭性和未分化恶性肿瘤亚群。

IF 9.1 1区医学

Cancer letters Pub Date : 2024-10-04 DOI: 10.1016/j.canlet.2024.217282

Natisha R. Field , Kristie-Ann Dickson , Najah T. Nassif , Deborah J. Marsh

{"title":"SMARCA4 and SMARCA2 co-deficiency: An uncommon molecular signature defining a subset of rare, aggressive and undifferentiated malignancies associated with defective chromatin remodeling","authors":"Natisha R. Field , Kristie-Ann Dickson , Najah T. Nassif , Deborah J. Marsh","doi":"10.1016/j.canlet.2024.217282","DOIUrl":"10.1016/j.canlet.2024.217282","url":null,"abstract":"<div><div>Genetic mutations and epigenetic modifications affecting multiple cancer-related genes occur synergistically to drive tumorigenesis. Across a wide spectrum of cancers, pathogenic changes have been identified in members of the SWItch/Sucrose Non-Fermentable complex including its two catalytic subunits, SMARCA4 and SMARCA2. During cancer development, it is not uncommon to lose the function of either SMARCA4 or SMARCA2, however, loss of both together has been reported to be synthetic lethal and therefore unexpected. Co-deficiency of SMARCA4 and SMARCA2 occurs as a pathognomonic feature of the early-onset ovarian cancer Small-cell carcinoma of the ovary, hypercalcemic type. The loss of both catalytic subunits is also described in other rare undifferentiated neoplasms including Thoracic <em>SMARCA4</em>-deficient undifferentiated tumors, Malignant rhabdoid tumors and dedifferentiated or undifferentiated carcinomas, predominantly of lung, gastrointestinal, and endometrial origin. This review provides the first extensive characterization of cancers with concurrent SMARCA4 and SMARCA2 loss through the discussion of shared clinical and molecular features. Further, we discuss the mechanisms triggering the loss of catalytic activity, the cellular processes that are dysfunctional as a consequence, and finally, current therapeutic candidates which may selectively target these cancers.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"605 ","pages":"Article 217282"},"PeriodicalIF":9.1,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380096","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

Exploring epigenetic dynamics unveils a super-enhancer-mediated NDRG1-β-catenin axis in modulating gemcitabine resistance in pancreatic cancer 表观遗传学动力学探索揭示了调节胰腺癌吉西他滨耐药性的超级增殖因子介导的 NDRG1-β-Catenin 轴。

IF 9.1 1区医学

Cancer letters Pub Date : 2024-10-02 DOI: 10.1016/j.canlet.2024.217284

Dianhui Wei , Lili Yuan , Xiaoli Xu , Chengsi Wu , Yiwen Huang , Lili Zhang , Jilong Zhang , Tiantian Jing , Yizhen Liu , Boshi Wang

{"title":"Exploring epigenetic dynamics unveils a super-enhancer-mediated NDRG1-β-catenin axis in modulating gemcitabine resistance in pancreatic cancer","authors":"Dianhui Wei , Lili Yuan , Xiaoli Xu , Chengsi Wu , Yiwen Huang , Lili Zhang , Jilong Zhang , Tiantian Jing , Yizhen Liu , Boshi Wang","doi":"10.1016/j.canlet.2024.217284","DOIUrl":"10.1016/j.canlet.2024.217284","url":null,"abstract":"<div><div>Chemoresistance remains a formidable challenge in pancreatic ductal adenocarcinoma (PDAC) treatment, necessitating a comprehensive exploration of underlying molecular mechanisms. This work aims to investigate the dynamic epigenetic landscape during the development of gemcitabine resistance in PDAC, with a specific focus on super-enhancers and their regulatory effects. We employed well-established gemcitabine-resistant (Gem-R) PDAC cell lines to perform high-throughput analyses of the epigenome, enhancer connectome, and transcriptome. Our findings revealed notable alterations in the epigenetic landscape and genome architecture during the transition from gemcitabine-sensitive to -resistant PDAC cells. Remarkably, we observed substantial plasticity in the activation status of super-enhancers, with a considerable proportion of these cis-elements becoming deactivated in chemo-resistant cells. Furthermore, we pinpointed the NDRG1 super-enhancer (NDRG1-SE) as a crucial regulator in gemcitabine resistance among the loss-of-function super-enhancers. NDRG1-SE deactivation induced activation of WNT/β-catenin signaling, thereby conferring gemcitabine resistance. This work underscores a NDRG1 super-enhancer deactivation-driven β-catenin pathway activation as a crucial regulator in the acquisition of gemcitabine-resistance. These findings advance our understanding of PDAC biology and provide valuable insights for the development of effective therapeutic approaches against chemoresistance in this malignant disease.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"605 ","pages":"Article 217284"},"PeriodicalIF":9.1,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375129","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