Cancer Science最新文献_第6页

Phospholipase D2 downregulates interleukin-1β secretion from tumor-associated macrophages to suppress bladder cancer progression. 磷脂酶D2能下调肿瘤相关巨噬细胞分泌的白细胞介素-1β，从而抑制膀胱癌的进展。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-11 DOI: 10.1111/cas.16393

Kazuki Hamada, Yoshiyuki Nagumo, Shuya Kandori, Bunpei Isoda, Shuhei Suzuki, Keisuke Sano, Shotaro Sakka, Kozaburo Tanuma, Satoshi Nitta, Masanobu Shiga, Hiromitsu Negoro, Bryan J Mathis, Yuji Funakoshi, Hiroyuki Nishiyama

{"title":"Phospholipase D2 downregulates interleukin-1β secretion from tumor-associated macrophages to suppress bladder cancer progression.","authors":"Kazuki Hamada, Yoshiyuki Nagumo, Shuya Kandori, Bunpei Isoda, Shuhei Suzuki, Keisuke Sano, Shotaro Sakka, Kozaburo Tanuma, Satoshi Nitta, Masanobu Shiga, Hiromitsu Negoro, Bryan J Mathis, Yuji Funakoshi, Hiroyuki Nishiyama","doi":"10.1111/cas.16393","DOIUrl":"https://doi.org/10.1111/cas.16393","url":null,"abstract":"The tumor microenvironment (TME) modulates therapeutic response and prognosis in patients with bladder cancer (BC). The roles of two phospholipase D (PLD) isoforms, PLD1 and PLD2 (hydrolysis of phosphatidylcholine to phosphatidic acid), in cancer cells have been well-studied in numerous cancer types, but their roles in the TME remain unclear. We used a mouse BC Pld2-KO carcinogenesis model and global transcriptomic analysis to reveal that PLD2 was significantly involved in BC progression through immunosuppressive pathways in the TME. We therefore focused on PLD2 and tumor-associated macrophages (TAMs), which were increased in Pld2-KO mice and further associated with poor prognoses in BC patients. In vitro, we found that Pld2-KO mouse TAMs had significantly enhanced proliferation, correlating closely with increased interleukin-1β (IL-1β) production. These results indicate that PLD2 suppresses BC progression by regulation of IL-1β secretion from TAMs in the TME, suggesting that PLD2 could serve as a potential therapeutic target for modifying the TME in BC.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Targeting CLK2 and serine/arginine-rich splicing factors inhibits multiple myeloma through downregulating RAE1 by nonsense-mediated mRNA decay mechanism. 靶向CLK2和富含丝氨酸/精氨酸的剪接因子可通过无义介导的mRNA衰减机制下调RAE1，从而抑制多发性骨髓瘤。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-11 DOI: 10.1111/cas.16387

Yang Liu, Yaping Liao, Shuping Lai, Xiaoyan Wu, Laoqi Liang, Yihao Zhang, Rongfang Wei, Yan Chen

{"title":"Targeting CLK2 and serine/arginine-rich splicing factors inhibits multiple myeloma through downregulating RAE1 by nonsense-mediated mRNA decay mechanism.","authors":"Yang Liu, Yaping Liao, Shuping Lai, Xiaoyan Wu, Laoqi Liang, Yihao Zhang, Rongfang Wei, Yan Chen","doi":"10.1111/cas.16387","DOIUrl":"https://doi.org/10.1111/cas.16387","url":null,"abstract":"Multiple myeloma (MM) is closely related to abnormal RNA splicing in its pathogenesis. CDC2-like kinase-2 (CLK2) regulates RNA splicing by phosphorylating serine/arginine-rich splicing factors (SRSFs), but the role of CLK2 in MM remains undefined. This study was to explore the role and mechanism of CLK2 in MM. Analyzing GEO datasets of MM patients found that high CLK2 expression predicted poor prognosis. Overexpression of CLK2 promoted the cell proliferation and cell cycle progression of MM cell ARP1 and H929. Knockdown or inhibition of CLK2 suppressed cell proliferation and induced cell apoptosis and cell cycle arrest in ARP1 and H929 cells in vitro. An MM xenograft tumor experiment showed that CLK2 overexpression promoted tumor growth, while CLK2 inhibition suppressed tumor growth in vivo. Mechanistic studies revealed that interfering CLK2 inhibited SRSF phosphorylation, and induced exon 9 skipping of RAE1, resulting in nonsense-mediated mRNA decay (NMD) of RAE1. In addition, RAE1 knockdown inhibited cell proliferation in ARP1 and H929 cells. Moreover, RAE1 overexpression promoted cell proliferation and cell cycle progression of ARP1 and H929 cells, and partially reversed the antitumor effect of CLK2 knockdown. Targeting CLK2 shows antitumor effects on MM partially through inhibiting SRSF phosphorylation and inducing NMD of RAE1. Therefore, targeting the CLK2/SRSFs/RAE1 axis could be a potential therapeutic strategy for MM.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

A population-based study using nomograms to predict overall and cancer-specific survival in HPV-associated CSCC. 一项基于人群的研究，使用提名图预测人乳头瘤病毒相关 CSCC 的总生存率和癌症特异性生存率。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-11 DOI: 10.1111/cas.16392

Suzheng Zheng, Yong He, Yanan Chen, Ming Chen, Hua Xian, Wai-Kit Ming, Yuzhen Jiang, Wong Hoi Shan, Tie Hang, Xiaoqi Tan, Jun Lyu, Liehua Deng

{"title":"A population-based study using nomograms to predict overall and cancer-specific survival in HPV-associated CSCC.","authors":"Suzheng Zheng, Yong He, Yanan Chen, Ming Chen, Hua Xian, Wai-Kit Ming, Yuzhen Jiang, Wong Hoi Shan, Tie Hang, Xiaoqi Tan, Jun Lyu, Liehua Deng","doi":"10.1111/cas.16392","DOIUrl":"https://doi.org/10.1111/cas.16392","url":null,"abstract":"Constructing and validating two nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) in cutaneous squamous cell carcinoma (CSCC) correlated with human papillomavirus (HPV) infection was the main goal of this study. We constructed predictive models for OS and CSS incidence in HPV infection-associated CSCC using information from 2238 patients in the Surveillance, Epidemiology, and End Results (SEER) database and screened the variables by LASSO regression, Cox univariate regression, and Cox multifactorial regression models, which were calibrated and validated by internal and external cohorts. Finally, all patients were categorized into intermediate-risk, low-risk, and high-risk groups based on the optimal threshold calculated from the total score. Multivariate analysis showed that HPV infection status, marital status, tumor metastatic stage, surgical status, radiotherapy status, lymph node biopsy, local lymph node dissection, primary tumor status, and bone metastasis were risk factors for OS and CSS. The C index, the time-dependent area under the receiver-operating characteristic curve, and the column-line diagrams of the calibration plot were among the excellent-performance metrics that were effectively displayed. Moreover, the decision curve analysis of the two nomograms consistently revealed their favorable net benefits spanning 1, 2, and 3 years. In addition, the survival curves indicate that each of the two risk classification systems clearly differentiates high, medium, and low risk groups. These meticulously crafted nomograms stand poised to serve as indispensable instruments in clinical practice, empowering clinicians to adeptly communicate with patients regarding their prognostic outlook over the forthcoming 1, 2, and 3 years.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Correction to "G protein pathway suppressor 2 suppresses gastric cancer by destabilizing epidermal growth factor receptor". 更正 "G 蛋白通路抑制因子 2 通过破坏表皮生长因子受体的稳定性来抑制胃癌"。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-05 DOI: 10.1111/cas.16391

引用次数: 0

The prognostic significance of MYC/BCL2 double expression in DLBCL in the genetic classification era. 基因分类时代 DLBCL 中 MYC/BCL2 双重表达的预后意义。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-04 DOI: 10.1111/cas.16377

Yi-Fan Wu, Qun-Hui Yuan, Hao-Rui Shen, Kai-Xin Du, Chun-Yu Shang, Yue Li, Xin-Yu Zhang, Jia-Zhu Wu, Rui Gao, Li Wang, Jian-Yong Li, Hua Yin, Jin-Hua Liang, Wei Xu

{"title":"The prognostic significance of MYC/BCL2 double expression in DLBCL in the genetic classification era.","authors":"Yi-Fan Wu, Qun-Hui Yuan, Hao-Rui Shen, Kai-Xin Du, Chun-Yu Shang, Yue Li, Xin-Yu Zhang, Jia-Zhu Wu, Rui Gao, Li Wang, Jian-Yong Li, Hua Yin, Jin-Hua Liang, Wei Xu","doi":"10.1111/cas.16377","DOIUrl":"https://doi.org/10.1111/cas.16377","url":null,"abstract":"Double expression (DE) is a World Health Organization-recognized adverse prognostic factor in diffuse large B-cell lymphoma (DLBCL). However, the prognostic value of DE in the genetic subtyping era and potential mechanisms remain to be explored. We enrolled 246 DLBCL patients diagnosed between December 2021 and September 2023 in a Jiangsu Province Hospital cohort and included 930 DLBCL patients from three published studies in an external cohort. Double-expression DLBCL (DEL) in the external cohort was mainly distributed in the OTHER subtype (42.0%), EZB subtype (28.3%), and MCD subtype (15.0%), whereas the MCD subtype exhibited the highest ratio of DEL. DEL was significantly related to unfavorable overall survival (OS) and progression-free survival (PFS) in DLBCL, but only in EZB and OTHER subtypes that DEL retained remarkably adverse impacts on survivals compared to non-DEL. We explored the prognostic value of clinical and genetic parameters in DEL patients and found only ST2 showed better OS than A53 in DEL patients, whereas the other subtypes showed no significant difference. DEL showed similarities with the MCD subtype in mutation profiles. Furthermore, RNA-sequencing analyses exhibited upregulation in tumor proliferation-related pathways in DEL patients, but downregulation in extracellular matrix organization, T-cell activation and proliferation, type II interferon production, and pathways associated with cell death might contribute to the poor outcomes of DEL patients.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Fibrocytes in tumor microenvironment: Identification of their fraction and novel therapeutic strategy. 肿瘤微环境中的纤维细胞：确定纤维细胞的组成和新型治疗策略

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-04 DOI: 10.1111/cas.16385

Atsushi Mitsuhashi, Yasuhiko Nishioka

{"title":"Fibrocytes in tumor microenvironment: Identification of their fraction and novel therapeutic strategy.","authors":"Atsushi Mitsuhashi, Yasuhiko Nishioka","doi":"10.1111/cas.16385","DOIUrl":"https://doi.org/10.1111/cas.16385","url":null,"abstract":"Fibrocytes were identified as bone marrow-derived myeloid cells that also have fibroblast-like phenotypes, such as ECM production and differentiation to myofibroblasts. Although fibrocytes are known to contribute to various types of tissue fibrosis, their functions in the tumor microenvironment are unclear. We focused on fibrocytes as pivotal regulators of tumor progression. Our previous studies have indicated that fibrocytes induce angiogenesis and cancer stem cell-like phenotypes by secreting various growth factors. In contrast, immune checkpoint inhibitor (ICI)-treated fibrocytes demonstrated antigen-presenting capacity and enhanced antitumor T cell proliferation. Taken together, these findings indicate that fibrocytes have multiple effects on tumor progression. However, the detailed phenotypes of fibrocytes have not been fully elucidated because the isolation of distinct fibrocyte clusters has not been achieved without culturing in ECM-coated conditions or intracellular staining of ECM. The development of single-cell analyses partially resolves these problems. Single-cell RNA sequences in CD45+ immune cells from tumor tissue identified ECM-expressing myeloid-like cells as distinct fibrocyte clusters. In addition, these findings enabled the isolation of tumor-infiltrating fibrocytes as CD45+CD34+ cells. These tumor-infiltrating fibrocytes demonstrated both antigen-presenting ability and differentiation into myofibroblast-like cancer-associated fibroblasts. Considering these functions of fibrocytes in tumor progression, molecular-targeting agents for the migration, activity, and differentiation of fibrocytes are promising therapeutic strategies. Furthermore, identification of specific cell surface markers and master regulators of fibrocytes will advance novel fibrocyte-targeting therapies. In this review, we discuss the multiple roles of tumor-infiltrating fibrocytes and novel cancer therapeutic strategies.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

METTL14 attenuates cancer stemness by suppressing ATF5/WDR74/β-catenin axis in gastric cancer. METTL14通过抑制胃癌中的ATF5/WDR74/β-catenin轴减轻癌症干性。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-04 DOI: 10.1111/cas.16381

Peiling Zhang, Hong Xiang, Qian Peng, Lujuan Ma, Chengyin Weng, Guolong Liu, Lin Lu

{"title":"METTL14 attenuates cancer stemness by suppressing ATF5/WDR74/β-catenin axis in gastric cancer.","authors":"Peiling Zhang, Hong Xiang, Qian Peng, Lujuan Ma, Chengyin Weng, Guolong Liu, Lin Lu","doi":"10.1111/cas.16381","DOIUrl":"https://doi.org/10.1111/cas.16381","url":null,"abstract":"Stemness is a key factor contributing to treatment failure in gastric cancer (GC). Methyltransferase-like 14 (METTL14) has been linked to various cancers, though its specific role in regulating stemness in GC remains undefined. In this study, we assessed METTL14 expression levels in GC tissues using public datasets and clinical specimens and investigated its impact on cell proliferation, metastasis, and stemness both in vitro and in vivo. Through m6A RNA immunoprecipitation (MeRIP) and luciferase reporter assays, we identified downstream targets of METTL14. Rescue assays were performed to examine whether METTL14 overexpression could reverse stemness in GC. We also explored the underlying mechanisms using chromatin immunoprecipitation (ChIP) and western blot analysis, focusing on the role of ATF5 and the upstream regulation of METTL14. Our findings show that lower METTL14 expression is associated with poorer overall survival in GC patients. Functionally, METTL14 knockdown enhanced stemness traits in GC cells. Mechanistically, METTL14 facilitated m6A modification, promoting the degradation of ATF5 mRNA. Overexpression of ATF5 reversed the stemness inhibition caused by METTL14 overexpression by increasing WDR74 transcription and enhancing β-catenin nuclear translocation. Furthermore, histone H3 lactylation at Lys18 was found to upregulate METTL14 expression. In conclusion, METTL14 knockdown promotes stemness in GC by mediating m6A modification of ATF5 mRNA, which activates the WDR74/β-catenin axis, making METTL14 a potential therapeutic target for gastric cancer treatment.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Camrelizumab combined with gemcitabine and apatinib in treating advanced PD-L1-positive biliary tract cancers. Camrelizumab 联合吉西他滨和阿帕替尼治疗晚期 PD-L1 阳性胆道癌。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-03 DOI: 10.1111/cas.16376

Yitong Tian, Changxian Li, Ke Jin, Ling Ma, Jiaguang Zhang, Xinyi Zhang, Wei You, Haoyang Shen, Yuting Ding, Hao Qian, Xiangcheng Li, Xiaofeng Chen

{"title":"Camrelizumab combined with gemcitabine and apatinib in treating advanced PD-L1-positive biliary tract cancers.","authors":"Yitong Tian, Changxian Li, Ke Jin, Ling Ma, Jiaguang Zhang, Xinyi Zhang, Wei You, Haoyang Shen, Yuting Ding, Hao Qian, Xiangcheng Li, Xiaofeng Chen","doi":"10.1111/cas.16376","DOIUrl":"https://doi.org/10.1111/cas.16376","url":null,"abstract":"The efficacy of combined chemotherapy and immunotherapy has previously been demonstrated in patients with biliary tract cancer. The aim of this study was to assess the efficacy and safety of camrelizumab in combination with gemcitabine and apatinib as a first- or second-line treatment for advanced programmed death-ligand 1 (PD-L1)-positive biliary tract cancer. This prospective, single-arm, and exploratory clinical trial aimed at recruiting 20 PD-L1-positive patients (tumor proportion score ≥1% or combined positive score ≥1) who met the inclusion criteria. Camrelizumab (200 mg) was administered in combination with gemcitabine (800 mg/m2) and apatinib (250 mg). The primary endpoint was the objective response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety. Fourteen patients were enrolled between September 2, 2020, and December 15, 2022. At the data cutoff on August 16, 2023, the median follow-up time was 11.4 months (interquartile range, 4.5-15.4), with one patient still undergoing treatment. Among the enrolled patients, six achieved a partial response, and four had stable disease. The ORR was 42.9% (95% confidence interval [CI], 17.7-71.1), and the DCR was 71.4% (95% CI, 41.9-91.6). The median PFS was 5.4 months (95% CI, 2.8-not reached), and the median OS was 13.5 months (95% CI, 5.7-not reached). The most frequent grade 3 or 4 treatment-related adverse event was neutropenia (n = 4, 29%). The combination of camrelizumab, gemcitabine, and apatinib showed promising efficacy and acceptable safety in patients with advanced PD-L1-positive biliary tract cancer.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Integrated machine learning to predict the prognosis of lung adenocarcinoma patients based on SARS-COV-2 and lung adenocarcinoma crosstalk genes. 基于SARS-COV-2和肺腺癌串联基因的综合机器学习预测肺腺癌患者的预后。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-03 DOI: 10.1111/cas.16384

Yanan Wu, Yishuang Cui, Xuan Zheng, Xuemin Yao, Guogui Sun

{"title":"Integrated machine learning to predict the prognosis of lung adenocarcinoma patients based on SARS-COV-2 and lung adenocarcinoma crosstalk genes.","authors":"Yanan Wu, Yishuang Cui, Xuan Zheng, Xuemin Yao, Guogui Sun","doi":"10.1111/cas.16384","DOIUrl":"https://doi.org/10.1111/cas.16384","url":null,"abstract":"Viruses are widely recognized to be intricately associated with both solid and hematological malignancies in humans. The primary goal of this research is to elucidate the interplay of genes between SARS-CoV-2 infection and lung adenocarcinoma (LUAD), with a preliminary investigation into their clinical significance and underlying molecular mechanisms. Transcriptome data for SARS-CoV-2 infection and LUAD were sourced from public databases. Differentially expressed genes (DEGs) associated with SARS-CoV-2 infection were identified and subsequently overlapped with TCGA-LUAD DEGs to discern the crosstalk genes (CGs). In addition, CGs pertaining to both diseases were further refined using LUAD TCGA and GEO datasets. Univariate Cox regression was conducted to identify genes associated with LUAD prognosis, and these genes were subsequently incorporated into the construction of a prognosis signature using 10 different machine learning algorithms. Additional investigations, including tumor mutation burden assessment, TME landscape, immunotherapy response assessment, as well as analysis of sensitivity to antitumor drugs, were also undertaken. We discovered the risk stratification based on the prognostic signature revealed that the low-risk group demonstrated superior clinical outcomes (p < 0.001). Gene set enrichment analysis results predominantly exhibited enrichment in pathways related to cell cycle. Our analyses also indicated that the low-risk group displayed elevated levels of infiltration by immunocytes (p < 0.001) and superior immunotherapy response (p < 0.001). In our study, we reveal a close association between CGs and the immune microenvironment of LUAD. This provides preliminary insight for further exploring the mechanism and interaction between the two diseases.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Zymogen granule protein 16B (ZG16B) is a druggable epigenetic target to modulate the mammary extracellular matrix. 酵母颗粒蛋白16B（ZG16B）是一种可用于调节乳腺细胞外基质的药物表观遗传靶标。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-03 DOI: 10.1111/cas.16382

Máté Lengyel, Ádám Molnár, Tamás Nagy, Sham Jdeed, Ildikó Garai, Zsolt Horváth, Iván P Uray

{"title":"Zymogen granule protein 16B (ZG16B) is a druggable epigenetic target to modulate the mammary extracellular matrix.","authors":"Máté Lengyel, Ádám Molnár, Tamás Nagy, Sham Jdeed, Ildikó Garai, Zsolt Horváth, Iván P Uray","doi":"10.1111/cas.16382","DOIUrl":"https://doi.org/10.1111/cas.16382","url":null,"abstract":"High tissue density of the mammary gland is considered a pro-tumorigenic factor, hence suppressing the stimuli that induce matrix buildup carries the potential for cancer interception. We found that in non-malignant mammary epithelial cells the combination of the chemopreventive agents bexarotene (Bex) and carvedilol (Carv) suppresses the zymogen granule protein 16B (ZG16B, PAUF) through an interaction of ARID1A with a proximal enhancer. Bex + Carv also reduced ZG16B levels in vivo in normal breast tissue and MDA-MB231 tumor xenografts. The relevance of ZG16B is underscored by ongoing clinical trials targeting ZG16B in pancreatic cancers, but its role in breast cancer development is unclear. In immortalized mammary epithelial cells, secreted recombinant ZG16B stimulated mitogenic kinase phosphorylation, detachment and mesenchymal characteristics, and promoted proliferation, motility and clonogenic growth. Highly concerted induction of specific laminin, collagen and integrin isoforms indicated a shift in matrix properties toward increased density and cell-matrix interactions. Exogenous ZG16B alone blocked Bex + Carv-mediated control of cell growth and migration, and antagonized Bex + Carv-induced gene programs regulating cell adhesion and migration. In breast cancer cells ZG16B induced colony formation and anchorage-independent growth, and stimulated migration in a PI3K/Akt-dependent manner. In contrast, Bex + Carv inhibited colony formation, reduced Ki67 levels, ZG16B expression and glucose uptake in MDA-MB231 xenografts. These data establish ZG16B as a druggable pro-tumorigenic target in breast cell transformation and suggest a key role of the matrisome network in rexinoid-dependent antitumor activity.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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