Cancer letters最新文献_第8页

PRTN3 promotes IL33/Treg-mediated tumor immunosuppression by enhancing the M2 polarization of tumor-associated macrophages in lung adenocarcinoma

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-22 DOI: 10.1016/j.canlet.2025.217584

Jiayu Jiang , Huilin Chen , Chunxing Zhao , Tong Li , Chen Zhang , Lingyu Ma , Huifang Su , Lei Ma , Zhaojun Duan , Qin Si , Tsung-Hsien Chuang , Chong Chen , Yunping Luo

{"title":"PRTN3 promotes IL33/Treg-mediated tumor immunosuppression by enhancing the M2 polarization of tumor-associated macrophages in lung adenocarcinoma","authors":"Jiayu Jiang , Huilin Chen , Chunxing Zhao , Tong Li , Chen Zhang , Lingyu Ma , Huifang Su , Lei Ma , Zhaojun Duan , Qin Si , Tsung-Hsien Chuang , Chong Chen , Yunping Luo","doi":"10.1016/j.canlet.2025.217584","DOIUrl":"10.1016/j.canlet.2025.217584","url":null,"abstract":"<div><div>The immunosuppressive tumor microenvironment (TME) shaped by tumor-associated macrophages (TAMs) is essential for lung adenocarcinoma (LUAD) immune tolerance and tumor progression. Here, we first reported that proteinase 3 (PRTN3) promoted the alternative activation (M2) of TAMs and enhanced IL33/regulatory T cells (Tregs)-mediated tumor immunosuppression in LUAD. Firstly, clinical analysis revealed PRTN3 was highly expressed in TAMs and correlated with the tumor progression and poor prognosis in LUAD patients. Meanwhile, by using the myeloid cells-specific <em>Prtn3</em>-knockout mouse model, we demonstrated <em>Prtn3</em> deficiency in macrophages remolded the immunosuppressive TME and suppressed tumor growth. The mechanism studies uncovered a novel signaling pathway that PRTN3 up-regulated IL33 expression in TAMs by suppressing AKT-mediated ubiquitinated degradation of FOXO1, which subsequently activated <em>Il33</em> transcription. Furthermore, lack of PRTN3 or FOXO1 in macrophages greatly restrained IL33-induced Treg differentiation. Importantly, selective knockout of <em>Prtn3</em> in macrophages significantly enhanced the antitumor effect of anti-PD1 therapy in the mouse model of LUAD. Thus, our work demonstrated that PRTN3 in macrophages, served as a key immunoregulator, contributed to impede the antitumor immune response through reinforcing the TAMs/Tregs crosstalk, which provided valuable insights to improve the immunotherapeutic effect by functional remodeling of TAMs to alleviate immunosuppression in LUAD.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"616 ","pages":"Article 217584"},"PeriodicalIF":9.1,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490864","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

Neurturin-Induced Activation of GFRA2-RET Axis Potentiates Pancreatic Cancer Glycolysis via Phosphorylated Hexokinase 2.

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-21 DOI: 10.1016/j.canlet.2025.217583

Ran Cui, Gaoming Wang, Fuguo Liu, Yongkun Wang, Zinan Zhao, Muladili Mutailipu, Huiling Mu, Xiaohua Jiang, Wenjun Le, Ludi Yang, Bo Chen

{"title":"Neurturin-Induced Activation of GFRA2-RET Axis Potentiates Pancreatic Cancer Glycolysis via Phosphorylated Hexokinase 2.","authors":"Ran Cui, Gaoming Wang, Fuguo Liu, Yongkun Wang, Zinan Zhao, Muladili Mutailipu, Huiling Mu, Xiaohua Jiang, Wenjun Le, Ludi Yang, Bo Chen","doi":"10.1016/j.canlet.2025.217583","DOIUrl":"https://doi.org/10.1016/j.canlet.2025.217583","url":null,"abstract":"<p><p>Pancreatic cancer, characterized by its insidious onset, high invasiveness, resistance to chemotherapy, and a grim prognosis, with a five-year survival rate hovering below 10%. The identification of novel therapeutic targets addressing tumor progression is therefore critically important. While perineural invasion (PNI) is recognized as a pathological hallmark and key driver of pancreatic cancer progression, its role in metabolic reprogramming of malignant cells has not been fully elucidated. Using integrated metabolomics approaches, we found perineural invasion in pancreatic cancer significantly enhancing glycolytic flux of pancreatic cancer. Our data delineate a neuroendocrine-paracrine signaling axis in which neurturin secreted by neuronal cells binds to the GFRA2 receptor on pancreatic cancer cells, inducing RET kinase recruitment and subsequent heterodimer assembly. This receptor tyrosine kinase complex phosphorylates hexokinase 2 (HK2) at the evolutionarily conserved Ser122 residue, augmenting its hexokinase activity, ultimately driving aerobic glycolysis flux and fueling pancreatic cancer growth. In vivo experiments corroborate our findings, revealing that neurturin blockade effectively halts pancreatic cancer progression and synergizes with RET inhibitors. Our research underscores neurturin as a promising therapeutic target for the treatment of pancreatic cancer.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217583"},"PeriodicalIF":9.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482361","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 “Regulation of the Nampt-mediated NAD salvage pathway and its therapeutic implications in pancreatic cancer [Cancer Lett. 379 (2016) 1–11]

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-20 DOI: 10.1016/j.canlet.2025.217562

Huai-Qiang Ju , Zhuo-Nan Zhuang , Hao Li , Tian Tian , Yun-Xin Lu , Xiao-Qiang Fan , Hai-Jun Zhou , Hai-Yu Mo , Hui Sheng , Paul J. Chiao , Rui-Hua Xu

引用次数: 0

Intracellular and extracellular activities of V-domain Ig-containing suppressor of T cell activation (VISTA) modulated by immunosuppressive factors of tumour microenvironment

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-20 DOI: 10.1016/j.canlet.2025.217581

Maryam Abooali , Stephanie Schlichtner , Xi Lei , Nijas Aliu , Sabrina Ruggiero , Sonia Loges , Martin Ziegler , Franziska Hertel , Anna-Lena Volckmar , Albrecht Stenzinger , Petros Christopoulos , Michael Thomas , Elena Klenova , N. Helge Meyer , Stergios Boussios , Nigel Heaton , Yoh Zen , Ane Zamalloa , Shilpa Chokshi , Luca Urbani , Vadim V. Sumbayev

{"title":"Intracellular and extracellular activities of V-domain Ig-containing suppressor of T cell activation (VISTA) modulated by immunosuppressive factors of tumour microenvironment","authors":"Maryam Abooali , Stephanie Schlichtner , Xi Lei , Nijas Aliu , Sabrina Ruggiero , Sonia Loges , Martin Ziegler , Franziska Hertel , Anna-Lena Volckmar , Albrecht Stenzinger , Petros Christopoulos , Michael Thomas , Elena Klenova , N. Helge Meyer , Stergios Boussios , Nigel Heaton , Yoh Zen , Ane Zamalloa , Shilpa Chokshi , Luca Urbani , Vadim V. Sumbayev","doi":"10.1016/j.canlet.2025.217581","DOIUrl":"10.1016/j.canlet.2025.217581","url":null,"abstract":"<div><div>V-domain Ig-containing suppressor of T cell activation (VISTA) is a unique immune checkpoint protein, which was reported to display both receptor and ligand activities. However, the mechanisms of regulation of VISTA activity and functions by factors of tumour microenvironment (TME) remain unclear and understanding these processes is required in order to develop successful personalised cancer immunotherapeutic strategies and approaches. Here we report for the very first time that VISTA interacts with another immune checkpoint protein galectin-9 inside the cell most likely facilitating its interaction with TGF-β-activated kinase 1 (TAK1). This process is required for protection of lysosomes, which is crucial for many cell types and tissues. We found that VISTA expression can be differentially controlled by crucial factors present in TME, such as transforming growth factor beta type 1 (TGF-β) and hypoxia as well as other factors activating hypoxic signalling. We confirmed that involvement of these important pathways modulated by TME differentially influences VISTA expression in different cell types. These networks include: TGF-β-Smad3 pathway, TAK1 (TGF-β-activated kinase 1) or apoptosis signal-regulating kinase 1 (ASK1)-induced activation of activating transcription factor 2 (ATF-2) and hypoxic signalling pathway. Based on this work we determined the five critical functions of VISTA and the role of TME factors in controlling (modulating or downregulating) VISTA expression.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"616 ","pages":"Article 217581"},"PeriodicalIF":9.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472441","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

LIN28B enhances the chemosensitivity of colon cancer cells via inducing genomic instability by upsetting the balance between the production and removal of reactive oxygen species LIN28B 通过破坏活性氧产生和清除之间的平衡，诱导基因组不稳定性，从而增强结肠癌细胞的化疗敏感性。

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-20 DOI: 10.1016/j.canlet.2025.217572

Tianzhen Wang , Mingjiao Weng , Kai Li , Guoli Li , Shijie Hu , Ziyi Hu , Yanping Li , Muhan Li , Di Wu , Zhigang Liang , Fei Yu , Guangyu Wang , Xiaobo Li

{"title":"LIN28B enhances the chemosensitivity of colon cancer cells via inducing genomic instability by upsetting the balance between the production and removal of reactive oxygen species","authors":"Tianzhen Wang , Mingjiao Weng , Kai Li , Guoli Li , Shijie Hu , Ziyi Hu , Yanping Li , Muhan Li , Di Wu , Zhigang Liang , Fei Yu , Guangyu Wang , Xiaobo Li","doi":"10.1016/j.canlet.2025.217572","DOIUrl":"10.1016/j.canlet.2025.217572","url":null,"abstract":"<div><div>Genomic instability is an enabling characteristic that allows cancer cells to acquire additional hallmarks of cancer through the accumulation of alterations in driver genes. Furthermore, it creates opportunities to enhance the sensitivity of cancer cells to chemotherapeutic agents targeting DNA, owing to the presence of incomplete DNA damage repair pathways. This study identifies LIN28B as a crucial regulator of colon cancer cells' sensitivity to DNA damage- or repair-related compounds by promoting genomic instability. LIN28B mechanistically reduces glutathione (GSH) synthesis and activity by inhibiting the expression of four GSH metabolic enzymes (GCLC, G6PD, GSTM4, and GSTT2B), thereby reducing the capacity of cells to eliminate reactive oxygen species (ROS). LIN28B enhances the proinflammatory signaling pathway in cancer cells through the upregulation of ARID3A, a transcription factor that transactivates PTGES and PTGES2, resulting in increased production of PGE2, a key inflammatory mediator that can elevate ROS generation. In conclusion, LIN28B altered the equilibrium of ROS production and elimination in colon cancer, resulting in elevated ROS levels and subsequent genomic instability.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"616 ","pages":"Article 217572"},"PeriodicalIF":9.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476323","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

Therapy resistance: Modulating evolutionarily conserved heat shock protein machinery in cancer

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-20 DOI: 10.1016/j.canlet.2025.217571

Ilona Skrabalak , Alicja Rajtak , Beata Malachowska , Natalia Skrzypczak , Karin A. Skalina , Chandan Guha , Jan Kotarski , Karolina Okla

引用次数: 0

SRSF12 deficiency enhances tumor innervation and accelerates pancreatic tumorigenesis

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-20 DOI: 10.1016/j.canlet.2025.217563

Min-Wei Yang , Qin-Yuan Jia , Da-Peng Xu , Yan-Nan Xu , Yan-Miao Huo , De-Jun Liu , Jian-Yu Yang , Xue-Liang Fu , Ding Ma , Zong-Hao Duan , Yi-Fan Yin , Xue-Shi-Yu Ma , Kan Xu , Rong Hua , Jun-Feng Zhang , Yong-Wei Sun , Wei Liu

{"title":"SRSF12 deficiency enhances tumor innervation and accelerates pancreatic tumorigenesis","authors":"Min-Wei Yang , Qin-Yuan Jia , Da-Peng Xu , Yan-Nan Xu , Yan-Miao Huo , De-Jun Liu , Jian-Yu Yang , Xue-Liang Fu , Ding Ma , Zong-Hao Duan , Yi-Fan Yin , Xue-Shi-Yu Ma , Kan Xu , Rong Hua , Jun-Feng Zhang , Yong-Wei Sun , Wei Liu","doi":"10.1016/j.canlet.2025.217563","DOIUrl":"10.1016/j.canlet.2025.217563","url":null,"abstract":"<div><div>The peripheral nervous system significantly determines the fate of solid tumors and their microenvironment. In neurotropic malignancies such as pancreatic and prostate cancer, denervation in animal models demonstrate significantly delays in tumor initiation and progression, underscoring the critical neural dependency of these cancers. While tumor innervation establishes a structural basis for the neuromodulatory effects, the degree of innervation exhibits marked heterogeneity across tumor types, and its regulatory mechanisms remain poorly characterized. In this study, we screened genes associated with innervation status in pancreatic cancer and identified the splicing factor <em>SRSF12</em> as a critical gene related to tumor innervation. In clinical samples, SRSF12 was expressed at low levels in pancreatic cancer tissues, and its downregulation was linked to poor prognosis in patients. Then we crossed <em>Kras</em> mutation and <em>Srsf12</em> knockout mice (<em>Kras</em><sup>G12D</sup> <em>Srsf12</em> <sup>fl/fl</sup>) together with <em>Srsf12</em> <sup>fl/fl</sup> <em>Pdx1</em><sup>cre</sup> mice and found that depletion of <em>Srsf12</em> accelerated <em>Kras</em>-driven pancreatic tumorigenesis and enhanced tumor innervation. Furthermore, we demonstrated that SRSF12 inhibits neurite outgrowth primarily by generating a LAMA3 splice isoform that lacks the fourth and fifth LG (G45) domains. Mechanistically, G45 promotes tumor innervation by activating ITGB1 and FAK in neurons. Together, our findings delineate SRSF12 as a novel suppressor of tumor innervation and pancreatic tumorigenesis, while also identifying a tumor-specific target for SRSF12-deficient pancreatic cancer.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"616 ","pages":"Article 217563"},"PeriodicalIF":9.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476329","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

The biological and technical challenges facing utilizing circulating tumor DNA in non-metastatic breast cancer patients

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-19 DOI: 10.1016/j.canlet.2025.217574

Zihang Zeng , Zongbi Yi , Binghe Xu

{"title":"The biological and technical challenges facing utilizing circulating tumor DNA in non-metastatic breast cancer patients","authors":"Zihang Zeng , Zongbi Yi , Binghe Xu","doi":"10.1016/j.canlet.2025.217574","DOIUrl":"10.1016/j.canlet.2025.217574","url":null,"abstract":"<div><div>Breast cancer is one of the most prevalent cancers and has emerged as a major global challenge. Circulating tumor DNA (ctDNA), a liquid biopsy method, overcomes the accessibility limitations of tissue-based testing and is widely used for monitoring minimal residual disease and molecular relapse, predicting prognosis, evaluating the response of neoadjuvant therapy, and optimizing treatment decisions in non-metastatic breast cancer. However, the application of ctDNA still faces many challenges. Here, we survey the clinical applications of ctDNA in non-metastatic breast cancer and discuss the significant biological and technical challenges of utilizing ctDNA. Importantly, we investigate potential avenues for addressing the challenges. In addition, emerging technologies, including fragmentomics detection, methylation sequencing, and long-read sequencing, have clinical potential and could be a future direction. Proper utilization of machine learning facilitates the identification of meaningful patterns from complex fragment and methylation profiles of ctDNA. There is still a lack of clinical trials focused on the subsets of ctDNA (e.g., circulating mitochondrial DNA), ctDNA-inferred drug-resistant clonal evolution, tumor heterogeneity, and ctDNA-guided clinical decision-making in non-metastatic breast cancer. Due to regional differences in the number of registered clinical trials, it is essential to enhance communication and foster global collaboration to advance the field.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"616 ","pages":"Article 217574"},"PeriodicalIF":9.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143455014","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

Evaluation and preservation of fertility in patients with hematologic malignancies

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-19 DOI: 10.1016/j.canlet.2025.217569

Xiang Wang , Ruihao Huang , Lei Liu , Xiaoqi Wang , Xi Zhang

引用次数: 0

SUMOylated hnRNPM suppresses PFKFB3 phosphorylation to regulate glycolysis and tumorigenesis SUMOylated hnRNPM 可抑制 PFKFB3 磷酸化，从而调节糖酵解和肿瘤发生。

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-19 DOI: 10.1016/j.canlet.2025.217573

Ya-Xian Zhong , Huan-Bin Zhao , Meng-Han Lian , Jia-Ming Shen , Cheng-Xiao Li , Hong-Ming Ma , Dan Xu , Guo-Qiang Chen , Cheng Zhang

{"title":"SUMOylated hnRNPM suppresses PFKFB3 phosphorylation to regulate glycolysis and tumorigenesis","authors":"Ya-Xian Zhong , Huan-Bin Zhao , Meng-Han Lian , Jia-Ming Shen , Cheng-Xiao Li , Hong-Ming Ma , Dan Xu , Guo-Qiang Chen , Cheng Zhang","doi":"10.1016/j.canlet.2025.217573","DOIUrl":"10.1016/j.canlet.2025.217573","url":null,"abstract":"<div><div>Heterogeneous nuclear ribonucleoprotein M (hnRNPM), a splicing regulatory factor with a majority of studies focused on its RNA-binding properties and effects on splicing outcome, is implicated in the progression of various kinds of human cancers, but its mechanisms remain largely enigmatic. Applying the global SUMOylated proteomic screening in colorectal cancer cells, herein we find that hnRNPM is SUMOylated at lysine 17 and Sentrin-specific protease 1 (SENP1) is essential for its de-SUMOylation. Although hnRNPM SUMOylation does not affect its known pre-mRNA splicing-related effects, more intriguingly, it remarkably influences lactate production. Mechanistically, SUMOylated hnRNPM interacts with 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) to affect its localization and inhibit its phosphorylation, thus suppressing glycolysis. Accordingly, SUMO-deficient hnRNPM promotes colorectal cancer cell proliferation and tumorigenesis in mice. Also, a negative correlation between hnRNPM SUMOylation and SENP1 expression or phosphorylated PFKFB3 levels can be found in CRC patient samples. These findings not only enhance our understanding of the multifaceted roles of hnRNPM in cancer biology but also open new avenues for the development of targeted therapies aimed at modulating hnRNPM SUMOylation.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"616 ","pages":"Article 217573"},"PeriodicalIF":9.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472443","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