Molecular Carcinogenesis最新文献_第10页

Elevated Polyamine Metabolism Activates Fibroblasts via GCN2 Activation and Generates Senescent Fibroblasts to Promote Tumor Formation and Progression. 多胺代谢升高通过GCN2激活成纤维细胞，产生衰老成纤维细胞，促进肿瘤的形成和进展。

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-11-01 Epub Date: 2025-08-19 DOI: 10.1002/mc.70034

Eric T Alexander, Katherine S Barone, Susan K Gilmour

{"title":"Elevated Polyamine Metabolism Activates Fibroblasts via GCN2 Activation and Generates Senescent Fibroblasts to Promote Tumor Formation and Progression.","authors":"Eric T Alexander, Katherine S Barone, Susan K Gilmour","doi":"10.1002/mc.70034","DOIUrl":"10.1002/mc.70034","url":null,"abstract":"GCN2 is one of the main sensors of amino acid starvation stress, and its activation in the stressful tumor microenvironment plays a crucial role in tumor survival. We hypothesized that elevated polyamine biosynthesis and subsequent depletion of precursor arginine in the tissue microenvironment activates GCN2 and alters stromal cell metabolism to support tumor cell survival and drive myeloid immunosuppressive function. To study the effect of elevated polyamine metabolism on fibroblast activation, we used the K6/ODC transgenic model of carcinogen-initiated, polyamine-promoted skin carcinogenesis. GCN2 loss significantly delayed tumor development and decreased tumor number and tumor burden in K6/ODC; GCN2-/- mice compared that in K6/ODC mice. Underlying dermal fibroblasts from nontumor bearing K6/ODC mice express elevated levels of genes associated with GCN2 activation and fibroblast activation. Expression of these genes was not elevated in K6/ODC; GCN2-/- dermis. In addition, K6/ODC mice have significantly more myeloid derived suppressor cells (MDSC) compared to normal littermates, and MDSCs were decreased in K6/ODC mice deficient in GCN2. Dermal fibroblasts cultured from K6/ODC transgenic mouse skin secrete increased levels of protumorigenic factors including senescence associated secretory phenotype (SASP) factors that stimulate invasiveness of stem-like epidermal tumorspheres as well as the polarization of M2-like macrophages. Using K6/ODC; p16-3MR mice in which senescent fibroblasts can be eliminated with ganciclovir treatment, carcinogen-initiated tumor development was greatly inhibited when senescent fibroblasts were eliminated in K6/ODC; p16-3MR mice. Our studies suggest a new paradigm in which cellular stress responses resulting from increased polyamine biosynthesis accelerate fibroblast activation and a senescence phenotype to create a protumorigenic microenvironment.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1872-1884"},"PeriodicalIF":3.2,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883238","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

Long Noncoding RNA MNX1-AS1 Promotes Tumorigenesis of Breast Cancer by Binding IGF2BP1 to Activate c-MET. 长链非编码RNA MNX1-AS1通过结合IGF2BP1激活c-MET促进乳腺癌的肿瘤发生

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-10-01 Epub Date: 2025-07-24 DOI: 10.1002/mc.70019

Jinrong Xie, Jianchun Gu, Wenjie Lv, Limin Cheng, Shuxian Chen, Ran Wu, Yan Liang, Meiling Zhu, Siyu Chen, Mawei Jiang, Jun Su

引用次数: 0

The Role and Mechanism of KIAA1429-Mediated m6A Modification in Pancreatic Adenocarcinoma. kiaa1429介导的m6A修饰在胰腺腺癌中的作用及机制

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-10-01 Epub Date: 2025-07-24 DOI: 10.1002/mc.70015

Pengbo Li, Yeting Lu, Zhen Zheng, Jiaming Lv, Jing Hu

{"title":"The Role and Mechanism of KIAA1429-Mediated m6A Modification in Pancreatic Adenocarcinoma.","authors":"Pengbo Li, Yeting Lu, Zhen Zheng, Jiaming Lv, Jing Hu","doi":"10.1002/mc.70015","DOIUrl":"10.1002/mc.70015","url":null,"abstract":"This study aimed to study the mechanism by which m6A methyltransferase, KIAA1429, affect pancreatic adenocarcinoma (PAAD) cell malignant behaviors in relation to N6-methyladenosine (m6A) modification. RT-qPCR, Western blot, immunohistochemistry (IHC), and m6A RNA immunoprecipitation (Me-RIP) assays were performed on PAAD tumor and adjacent non-tumor tissues (n = 39) to detect KIAA1429, AKT2 mRNA and protein levels, as well as overall tissue RNA m6A methylation levels. Tumor cells were transfected with siRNA targeting KIAA1429 (si-KIAA1429) or plasmids overexpressing AKT2 (oe-AKT2). Cell activities were assessed, followed by assessment of autophagic flux using the mRFP-GFP-LC3 reporter. In PAAD tissues and cell lines, KIAA1429 was substantially expressed. In PAAD patients, this expression was linked to a considerably lower overall and disease-specific survival rate. KIAA1429 knockdown inhibited PAAD cell malignant behaviors and promoted autophagy. Mechanistically, KIAA1429 mediated AKT2 m6A modification to enhance AKT2 mRNA stability and upregulate AKT2 expression, partially reversing the mediating effects of KIAA1429 knockdown on PAAD cell malignant behaviors and autophagy. KIAA1429 knockdown also inhibited PAAD tumor growth in vivo. KIAA1429 promotes PAAD cell malignant behaviors while inhibiting autophagy activity by mediating AKT2 m6A modification and enhancing AKT2 expression.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1667-1682"},"PeriodicalIF":3.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708309","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

KIF4A Inhibits Ferroptosis in Glioblastoma via the CHMP4B/GPX4 Axis and Promotes Temozolomide Resistance. KIF4A通过CHMP4B/GPX4轴抑制胶质母细胞瘤铁凋亡，促进替莫唑胺耐药性

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-10-01 Epub Date: 2025-07-24 DOI: 10.1002/mc.70006

Xinan Shen, Honglei Cheng, Jiarong Zheng, Yihan Xia, Yongdong Li, Quanquan Guo, Zhicheng Zhang, Nanheng Yin, Yongshun Liu, Jun Dong, Yuntian Shen

{"title":"KIF4A Inhibits Ferroptosis in Glioblastoma via the CHMP4B/GPX4 Axis and Promotes Temozolomide Resistance.","authors":"Xinan Shen, Honglei Cheng, Jiarong Zheng, Yihan Xia, Yongdong Li, Quanquan Guo, Zhicheng Zhang, Nanheng Yin, Yongshun Liu, Jun Dong, Yuntian Shen","doi":"10.1002/mc.70006","DOIUrl":"10.1002/mc.70006","url":null,"abstract":"Glioblastoma (GBM) is the most malignant primary brain tumor in adults. Temozolomide (TMZ) stands for the first-line chemotherapeutic agent against GBM. TMZ resistance is an important factor contributing to the poor prognosis of GBM, but the underlying molecular mechanisms are unclear. Previous studies have suggested that KIF4A may be an indicator of poor prognosis in glioma patients, but the association of KIF4A with TMZ resistance has never been investigated. The detection of ferroptosis levels in GBM cells was accomplished through the utilization of ROS, MDA, JC-1, and Western blot analysis. The assessment of TMZ resistance was performed through the implementation of CCK8, cell cloning, and cell cycle analysis. The identification of downstream targets of KIF4A was facilitated by protein profiling and immunofluorescence. KIF4A inhibits ferroptosis in GBM cells through the CHMP4B/GPX4 axis and promotes TMZ resistance. Knockdown of KIF4A or CHMP4B sensitized GBM cells to chemotherapy. In addition, KIF4A induced epithelial-mesenchymal transition in GBM cells, which synergistically promoted TMZ resistance.The present study elucidates a novel mechanism of TMZ resistance in glioblastoma through the CHMP4B/GPX4 axis. Based on these findings, targeting KIF4A may offer a potential new strategy against GBM.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1650-1666"},"PeriodicalIF":3.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708307","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

CircLPP Activates the Wnt/β-Catenin Signaling Pathway via the miR-665/Wnt3a Axis and Promotes Proliferation and Metastasis in Colorectal Cancer. CircLPP通过miR-665/Wnt3a轴激活Wnt/β-Catenin信号通路，促进结直肠癌的增殖和转移

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-10-01 Epub Date: 2025-08-12 DOI: 10.1002/mc.70020

Hong Gao, Qingguo Liu, Yuting Li, Xudong Sun, Jianquan Liu, Qihang Hu, Tao Jiang, Jun Song

引用次数: 0

FBXW5 Promotes Epithelial-Mesenchymal Transition in Lung Adenocarcinoma Through the KLF13/TROAP Signaling Pathway. FBXW5通过KLF13/TROAP信号通路促进肺腺癌上皮-间质转化

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-10-01 Epub Date: 2025-07-22 DOI: 10.1002/mc.70018

Wen Wang, Shaungru Tian, Yuxin Ou, Jinsong Yang

{"title":"FBXW5 Promotes Epithelial-Mesenchymal Transition in Lung Adenocarcinoma Through the KLF13/TROAP Signaling Pathway.","authors":"Wen Wang, Shaungru Tian, Yuxin Ou, Jinsong Yang","doi":"10.1002/mc.70018","DOIUrl":"10.1002/mc.70018","url":null,"abstract":"Epithelial-mesenchymal transition (EMT) has been shown to facilitate lung adenocarcinoma (LUAD) progress, and KLF13 inhibits tumor progression in various cancers. We intended to explore the mechanisms of KLF13 on EMT in LUAD. The biological functions (including cell viability, invasion, migration, and EMT) were checked using CCK-8, Transwell, and wound healing. The KLF13 and EMT markers levels were detected by immunohistochemistry. Interaction between KLF13 and TROAP promoter was probed by ChIP and dual luciferase reporter gene assay. The association between FBXW5 and KLF13 was verified by CoIP. RT-qPCR or Western blot was employed to check the expressions of FBXW5, KLF13, TROAP, and EMT markers. A xenograft tumor model was constructed to determine the growth of LUAD cells. KLF13 was lowly expressed in LUAD tissues and cells. KLF13 inhibited the invasion, migration, and EMT of LUAD cells. KLF13 suppressed TROAP transcription, and overexpression of TROAP reversed the inhibitory effect of KLF13 on the biological functions of LUAD cells. FBXW5 promoted KLF13 ubiquitinated degradation, and the knockdown of FBXW5 promoted KLF13 to inhibit LUAD cell progression. FBXW5 promoted KLF13 ubiquitinated degradation, which downregulated KLF13 to increase TROAP transcription, thereby facilitating EMT in LUAD.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1638-1649"},"PeriodicalIF":3.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691038","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

B4GALT3 as a Key Glycosyltransferase Gene in Multiple Myeloma Progression: Insights From Bioinformatics, Machine Learning, and Experimental Validation. B4GALT3是多发性骨髓瘤进展中的关键糖基转移酶基因：来自生物信息学、机器学习和实验验证的见解。

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-10-01 Epub Date: 2025-07-13 DOI: 10.1002/mc.70013

Apeng Yang, Mengying Ke, Lin Feng, Ye Yang, Junmin Chen, Zhiyong Zeng

{"title":"B4GALT3 as a Key Glycosyltransferase Gene in Multiple Myeloma Progression: Insights From Bioinformatics, Machine Learning, and Experimental Validation.","authors":"Apeng Yang, Mengying Ke, Lin Feng, Ye Yang, Junmin Chen, Zhiyong Zeng","doi":"10.1002/mc.70013","DOIUrl":"10.1002/mc.70013","url":null,"abstract":"Glycosylation abnormalities are critical in the progression of various cancers. However, their role in the onset and prognosis of multiple myeloma (MM) remains underexplored. This study aims to identify glycosyltransferase (GT)-related biomarkers and investigate their underlying mechanisms in MM. GT-related genes were extracted from the MMRF-CoMMpass and GSE57317 data sets. Potential biomarkers were identified using Cox regression and Lasso analyses. A glycosyltransferase-related prognostic model (GTPM) was developed by evaluating 113 machine learning algorithm combinations. The expression of B4GALT3, a key gene identified through this model, was analyzed in MM bone marrow samples using immunohistochemistry, quantitative PCR, and Western blot. Functional roles of B4GALT3 in MM cell behavior were assessed through knockdown experiments, and its mechanism of action was investigated. The GTPM stratified MM patients into high- and low-risk groups, with significantly better survival in the low-risk group (HR = 55.94, 95% CI = 40.48-77.31, p < 0.001). The model achieved AUC values of 0.98 and 0.99 for 1- and 3-year overall survival, outperforming existing gene signatures (including EMC92, UAMS70, and UAMS17). B4GALT3 expression was significantly elevated in advanced MM stages (p < 0.001) and correlated with poorer survival. Knockdown of B4GALT3 reduced MM cell proliferation, invasion, and increased apoptosis. Mechanistic analyses revealed that B4GALT3 modulates MM cell behavior via the Wnt/β-catenin/GRP78 pathway, primarily by regulating endoplasmic reticulum (ER) stress. This study developed a novel GTPM for predicting survival in MM and identified B4GALT3 as a key gene influencing disease progression. Experimental evidence highlights B4GALT3's role in modulating ER stress and Wnt/β-catenin pathways, positioning it as a potential prognostic biomarker and therapeutic target in MM.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1595-1608"},"PeriodicalIF":3.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626747","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

Combined Inhibition of XPO1 and DNA Methylation Exerts Synergistic Effects in DLBCL. XPO1和DNA甲基化联合抑制在DLBCL中发挥协同作用。

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-10-01 Epub Date: 2025-07-13 DOI: 10.1002/mc.70014

Qi Li, Xiaofeng Xue, Si Chen, Xinyun Zhang, Yuchen Zhang, Ruijing Hu, Xinyuan Zhang, Linlin Qin, Menglu Chen, Wenzhuo Zhuang, Bingzong Li

{"title":"Combined Inhibition of XPO1 and DNA Methylation Exerts Synergistic Effects in DLBCL.","authors":"Qi Li, Xiaofeng Xue, Si Chen, Xinyun Zhang, Yuchen Zhang, Ruijing Hu, Xinyuan Zhang, Linlin Qin, Menglu Chen, Wenzhuo Zhuang, Bingzong Li","doi":"10.1002/mc.70014","DOIUrl":"10.1002/mc.70014","url":null,"abstract":"Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma characterized by high rates of relapse and limited responsiveness to standard chemotherapy. Selinxor, a selective inhibitor of XPO1, exhibited antitumor activity in various cancers. However, clinical trial results revealed that selinexor monotherapy exhibited unsatisfactory efficacy in DLBCL. Our study indicated that XPO1 expression was increased in DLBCL and was correlated with poor outcomes of DLBCL patients. Comprehensive proteomic and transcriptomics analysis showed that selinexor has significant impacts on various biological processes in DLBCL. Furthermore, we explored combination strategies involving selinexor to enhance DLBCL treatment. We examined the combined effects of selinexor with decitabine (DAC) and lenalidomide (LEN), and found that selinexor exhibited a synergistic effect with DAC against DLBCL. Further analysis revealed that DAC exerted a synergistic antitumor effect with selinexor by reversing the DNMT1 expression and DNA methylation alterations induced by selinexor. Overall, these findings provided valuable insights into the global impact of selinexor on DLBCL. The combination therapy of selinexor and DAC emerges as a highly promising strategy for effectively treating DLBCL, holding great potential for clinical application.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1609-1619"},"PeriodicalIF":3.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626748","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

Venetoclax Synergizes With Regorafenib for Colorectal Cancer by Targeting BCL-2. 通过靶向BCL-2， Venetoclax与Regorafenib协同治疗结直肠癌

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-10-01 Epub Date: 2025-07-24 DOI: 10.1002/mc.70017

Lijun Zhu, Weicheng Wang, Yuwen Dong, Xiao Han, Wei Zhang, Zhonghua Zhang, Wenjie Guo, Yanhong Gu

引用次数: 0

The Contradictory Effects of SPTLC1 on Clear Cell Renal Carcinoma Sensitivity to Sunitinib Mediated by Androgen Receptor. SPTLC1在雄激素受体介导的透明细胞肾癌舒尼替尼敏感性中的矛盾作用。

IF 3.2 2区医学

Molecular Carcinogenesis Pub Date : 2025-10-01 Epub Date: 2025-08-12 DOI: 10.1002/mc.70023

Liqiong Liao, Zhixiong Zhang, Zhenhua Li, Daqiang Wei, Yanni Xie, Haodong Zeng, Hongyang Zhao, Yuhao Zhou, Di Gu, Xiaolu Duan

{"title":"The Contradictory Effects of SPTLC1 on Clear Cell Renal Carcinoma Sensitivity to Sunitinib Mediated by Androgen Receptor.","authors":"Liqiong Liao, Zhixiong Zhang, Zhenhua Li, Daqiang Wei, Yanni Xie, Haodong Zeng, Hongyang Zhao, Yuhao Zhou, Di Gu, Xiaolu Duan","doi":"10.1002/mc.70023","DOIUrl":"10.1002/mc.70023","url":null,"abstract":"Serine palmitoyltransferase long chain-1 (SPTLC1) is a key enzyme in ceramide synthesis, previously identified as a suppressor of tumorigenesis in clear cell renal carcinoma (ccRCC). Although elevated levels of very long-chain ceramides are associated with the canonical multidrug resistance in ccRCC, the specific role of SPTLC1 in modulating the sensitivity of ccRCC to sunitinib remains unclear. In this study, we found that SPTLC1 overexpression could enhance the sensitivities of 786-O and OSRC-2 cells to sunitinib via downregulating CerS2 expression and long-chain ceramide levels. In contrast, SPTLC1 upregulated CerS2 expression and long-chain ceramide levels in A498 cells, yet without a significant impact on its sensitivity to sunitinib. In addition, overexpression of CerS2 significantly attenuated SPTLC1-enhanced sensitivities of 786-O and OSRC-2 cells to sunitinib, whereas CerS2 knockdown obviously enhanced the sensitivity of A498 cells to sunitinib. Moreover, androgen receptor (AR) expression was significantly decreased in SPTLC1-overexpressed 786-O cells and forced AR expression could obviously attenuate the downregulation of CerS2 expression induced by SPTLC1 in 786-O cells, whereas opposite results were observed in A498 cells, suggesting that the contradictory effects of SPTLC1 on CerS2 expression were modulated by AR. Taken together, our results demonstrated that the contradictory effects of SPTLC1 on clear cell renal carcinoma sensitivity to sunitinib were caused by AR-mediated CerS2 expression, thus revealing a novel role and mechanism of SPTLC1 in the regulation of ccRCC sensitivity to sunitinib.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1778-1791"},"PeriodicalIF":3.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822111","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