Carcinogenesis最新文献_第2页

Reactions of [13C]-Labelled Tobacco Smoke with DNA to Generate Selected Adducts Formed Without Metabolic Activation. [13C]标记的烟草烟雾与DNA反应生成未经代谢激活形成的选定加合物。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-02-26 DOI: 10.1093/carcin/bgaf008

Mei-Kuen Tang, Trevor Ostlund, Nour F Dameh, Aleksandra Alcheva, Jerry D Cohen, Adrian D Hegeman, Steven G Carmella, Irina Stepanov, Stephen S Hecht

{"title":"Reactions of [13C]-Labelled Tobacco Smoke with DNA to Generate Selected Adducts Formed Without Metabolic Activation.","authors":"Mei-Kuen Tang, Trevor Ostlund, Nour F Dameh, Aleksandra Alcheva, Jerry D Cohen, Adrian D Hegeman, Steven G Carmella, Irina Stepanov, Stephen S Hecht","doi":"10.1093/carcin/bgaf008","DOIUrl":"10.1093/carcin/bgaf008","url":null,"abstract":"DNA adducts are central in the carcinogenic process because they can cause miscoding leading to permanent mutations in important genes involved in carcinogenesis. While it is known that tobacco smoking leads to increased levels of multiple DNA adducts, most DNA adducts detected to date in humans cannot be explicitly attributed to smoking but instead have various possible exogenous and endogenous sources. We plan to probe the tobacco source of DNA adducts by providing carbon-13 labelled ([13C]-labelled) cigarettes to smokers and analyzing [13C]-labelled DNA adducts in their oral cells to determine which adducts arise from smoking. Prior to conducting studies in humans, we first report here proof-of-principle machine smoking experiments to evaluate carbon isotopologues of (a) selected carbonyls and (b) DNA adducts resulting from direct exposure of cigarette smoke vapor-phase to calf-thymus DNA. The smoke of the study cigarettes, made from a 50:50 mixture of [13C]-labelled tobacco and a popular commercial tobacco, yielded similar concentrations of carbonyl compounds and their respective DNA adducts compared with the smoke of 1R6F reference cigarettes and the popular brand of cigarettes. We detected [13C]-isotopologues of DNA adducts such as 1,N6-etheno-dA, (8R/S)-3-(2'-deoxyribos-1-yl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2-a]purine-10(3H)-one (γ-OH-Acr-dG), and (6S,8S and 6R,8R)-3-(2'-deoxyribos-1-yl)-5,6,7,8-tetrahydro-8-hydroxy-6-methylpyrimido[1,2-a]purine-10(3H)-one [(6S,8S)-γ-OH-Cro-dG and (6R,8R)-γ-OH-Cro-dG], proving that they have a direct source from tobacco smoke and providing important new insights regarding their mechanisms of formation. These unique results form the basis for further studies in cell culture and in cigarette smokers to establish how carcinogens in tobacco smoke cause DNA adduct formation.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

TNBC molecular subtypes and potential detection targets for biological therapy indications. TNBC分子亚型及生物治疗适应症的潜在检测靶点。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-02-20 DOI: 10.1093/carcin/bgaf006

Yanchuan Zhang, Qinghua Li, Jie Lan, Guojing Xie, Guangjie Zhang, Junhao Cui, Ping Leng, Yingshuang Wang

{"title":"TNBC molecular subtypes and potential detection targets for biological therapy indications.","authors":"Yanchuan Zhang, Qinghua Li, Jie Lan, Guojing Xie, Guangjie Zhang, Junhao Cui, Ping Leng, Yingshuang Wang","doi":"10.1093/carcin/bgaf006","DOIUrl":"https://doi.org/10.1093/carcin/bgaf006","url":null,"abstract":"Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer associated with poor prognosis. While chemotherapy remains the conventional treatment approach, its efficacy is limited and often accompanied by significant toxicity. Advances in precision-targeted therapies have expanded treatment options for TNBC, including immunotherapy, poly (ADP-ribose) polymerase inhibitors, androgen receptor inhibitors, cell cycle-dependent kinase inhibitors, and signaling pathway inhibitors. However, the heterogeneous nature of TNBC contributes to variations in treatment outcomes, underscoring the importance of identifying intrinsic molecular subtypes for personalized therapy. Additionally, due to patient-specific variability, the therapeutic response to targeted treatments is inconsistent. This highlights the need to strategize patients based on potential therapeutic targets for targeted drugs to optimize treatment strategies. This review summarizes the classification strategies and immunohistochemical (IHC) biomarkers for TNBC subtypes, along with potential targets for identifying indications for targeted drug therapy. These insights aim to support the development of personalized treatment approaches for TNBC patients.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Dysregulation of G6PD by HPV E6 exacerbates cervical cancer by activating the STAT3/PLOD2 pathway. HPV E6对G6PD的失调通过激活STAT3/PLOD2通路加重宫颈癌。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-02-13 DOI: 10.1093/carcin/bgaf005

Jie Zhang, Wei Dong, Qin Yang, Li-Na Liu, Xi-Lun Cai, Dan Wang, Guo-Ji Yan, Yan-Bin Xiyang, Tao Hu, Jie Zhang

{"title":"Dysregulation of G6PD by HPV E6 exacerbates cervical cancer by activating the STAT3/PLOD2 pathway.","authors":"Jie Zhang, Wei Dong, Qin Yang, Li-Na Liu, Xi-Lun Cai, Dan Wang, Guo-Ji Yan, Yan-Bin Xiyang, Tao Hu, Jie Zhang","doi":"10.1093/carcin/bgaf005","DOIUrl":"https://doi.org/10.1093/carcin/bgaf005","url":null,"abstract":"High-risk human papillomavirus (HPV) infection is strongly linked to the initiation and progression of cervical cancer, yet the precise molecular mechanisms involved remain partially understood. This investigation examined differential protein expression profiles in various cohorts, including healthy controls and HPV-positive cervical cancer patients with different expression levels of glucose-6-phosphate dehydrogenase (G6PD), shedding light on the dysregulation of oncogenic proteins by HPV. Proteomic analysis of cervical tissues revealed specific protein signatures, indicating significant upregulation of HPV E6, G6PD, STAT3, phosphorylated STAT3, and procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) in HPV-infected cervical cancer tissues and cell lines. Functional experiments, involving the manipulation of G6PD and STAT3 activities in cervical cancer cells with HPV E6 modulation, demonstrated that dysregulated G6PD enhanced cell proliferation, migration, and invasion while suppressing apoptosis, primarily through the STAT3/PLOD2 pathway. Integrating these findings with the existing literature underscores the role of G6PD as an oncogene, potentially under STAT3 regulation, and highlights the role of PLOD2 as a pivotal factor in cervical cancer progression. This study also proposed a mechanism in which HPV E6-induced dysregulation of G6PD activates the STAT3-PLOD2 axis to promote cervical cancer progression. Understanding the intricate interplay between HPV E6, G6PD, STAT3, and PLOD2 offers valuable insights into the molecular landscape of cervical cancer. These findings may pave the way for targeted therapeutic approaches aimed at disrupting this axis to mitigate the progression of cervical cancer.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Role of the nucleotide excision repair function of CETN2 in the inhibition of the sensitivity of hepatocellular carcinoma cells to oxaliplatin. CETN2核苷酸切除修复功能在抑制肝癌细胞对奥沙利铂敏感性中的作用

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-02-13 DOI: 10.1093/carcin/bgaf003

Hengcheng Tang, Huaduan Zi, Donghu Zhou, Yanmeng Li, Xiaojin Li, Zhibin Chen, Qianyu Zhu, Qin Ouyang, Pingping He, Sisi Chen, Yanling Li, Jiang Long, Jian Huang

{"title":"Role of the nucleotide excision repair function of CETN2 in the inhibition of the sensitivity of hepatocellular carcinoma cells to oxaliplatin.","authors":"Hengcheng Tang, Huaduan Zi, Donghu Zhou, Yanmeng Li, Xiaojin Li, Zhibin Chen, Qianyu Zhu, Qin Ouyang, Pingping He, Sisi Chen, Yanling Li, Jiang Long, Jian Huang","doi":"10.1093/carcin/bgaf003","DOIUrl":"https://doi.org/10.1093/carcin/bgaf003","url":null,"abstract":"Resistance to platinum-based chemotherapy agents like oxaliplatin (OXA) poses significant challenges in the treatment of cancers such as hepatocellular carcinoma (HCC). Centrin 2 (CETN2), which functions in nucleotide excision repair (NER) of DNA damage, is overexpressed in HCC. We investigated the potential role of CETN2 in modulating the sensitivity of HCC cells to OXA. CETN2 expression correlated with decreased OXA sensitivity in Huh7 and Hep3B HCC cell lines. CETN2 forms a complex with XPC, which is crucial for the initial DNA damage recognition in NER, thereby enhancing NER and reducing the efficacy of OXA. siRNA-mediated knockdown of CETN2 increased OXA-induced cytotoxicity and apoptosis, confirming its role in chemoresistance. Moreover, overexpression of CETN2 inhibited OXA-induced DNA damage, an effect partially reversed by XPC knockdown. Our findings highlight CETN2 as a potential biomarker and therapeutic target in overcoming OXA resistance in HCC and suggest the possibility for CETN2 inhibitors in enhancing chemotherapeutic efficacy in the treatment of HCC.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Integrative functional screen of genomic loci uncovers CCND2 and its genetic regulatory mechanism in colorectal cancer development. 基因组位点综合功能筛选揭示CCND2及其在结直肠癌发生中的遗传调控机制

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae078

Bin Li, Mei Wu, Hui Geng, Yan Li, Zhirui Chen, Zequn Lu, Xu Chen, Qiuhong Wang, Shuxin Song, Xiangpan Li, Xu Zhu, Yongchang Wei, Ying Zhu, Xiaoping Miao, Jianbo Tian, Jiuyang Liu, Chaoqun Huang, Xiaojun Yang

{"title":"Integrative functional screen of genomic loci uncovers CCND2 and its genetic regulatory mechanism in colorectal cancer development.","authors":"Bin Li, Mei Wu, Hui Geng, Yan Li, Zhirui Chen, Zequn Lu, Xu Chen, Qiuhong Wang, Shuxin Song, Xiangpan Li, Xu Zhu, Yongchang Wei, Ying Zhu, Xiaoping Miao, Jianbo Tian, Jiuyang Liu, Chaoqun Huang, Xiaojun Yang","doi":"10.1093/carcin/bgae078","DOIUrl":"10.1093/carcin/bgae078","url":null,"abstract":"Although genome-wide association studies have identified dozens of loci associated with colorectal cancer (CRC) susceptibility, the causal genes or risk variants within these loci and their biological functions often remain elusive. Recently, the genomic locus 12p13.32, with the tag single-nucleotide polymorphism rs10774214, was identified as a crucial CRC risk locus in Asian populations. However, the functional mechanism of this region has not been fully elucidated. Here, we applied a high-throughput RNA interference approach in CRC cell lines to interrogate the function of genes in this genomic region. Multiple genes were found to affect cell functions, with CCND2 having the most significant effect as an oncogene. Moreover, overexpressed CCND2 could promote CRC cell proliferation. Subsequently, by integrating a fine-mapping analysis and multi-ancestry large-scale population cohorts consisting of 14 358 CRC cases and 34 251 healthy controls, we identified a regulatory variant rs4477507-T that contributed to an increased CRC risk in populations from China (odds ratio = 1.16, 95% confidence interval = 1.11-1.22, P = 4.45 × 10-10) and Europe (odds ratio = 1.17, 95% confidence interval = 1.12-1.21, P = 1.65 × 10-14). Functional characterization of the variant demonstrated that it could act as an allele-specific enhancer to distally facilitate the expression of CCND2 mediated by the transcription factor TEAD4. Overall, our study underscores the essential role of CCND2 in CRC development and delineates its regulatory mechanism mediated by rs4477507, establishing an epidemiological and biological link between genetic variation and CRC pathogenesis.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 benzo[a]pyrene-induced DNA adduct in buccal cells of smokers by black raspberry lozenges. 黑覆盆子润喉糖抑制吸烟者口腔细胞中苯并[a]芘诱导的 DNA 加合物

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae067

Kun-Ming Chen, Nicolle M Krebs, Yuan-Wan Sun, Dongxiao Sun, Jiangang Liao, Lisa Reinhart, Jacek Krzeminski, Shantu Amin, Gary Stoner, Susan R Mallery, Karam El-Bayoumy

{"title":"Inhibition of benzo[a]pyrene-induced DNA adduct in buccal cells of smokers by black raspberry lozenges.","authors":"Kun-Ming Chen, Nicolle M Krebs, Yuan-Wan Sun, Dongxiao Sun, Jiangang Liao, Lisa Reinhart, Jacek Krzeminski, Shantu Amin, Gary Stoner, Susan R Mallery, Karam El-Bayoumy","doi":"10.1093/carcin/bgae067","DOIUrl":"10.1093/carcin/bgae067","url":null,"abstract":"Using LC-MS/MS analysis we previously showed for the first time (Carcinogenesis 43:746-753, 2022) that levels of DNA damage induced by benzo[a]pyrene (B[a]P), an oral carcinogen and tobacco smoke (TS) constituent, were significantly higher in buccal cells of smokers than those in nonsmokers; these results suggest the potential contribution of B[a]P in the development of oral squamous cell carcinoma (OSCC) in humans. Treating cancers, including OSCC, at late stages, even with improved targeted therapies, continues to be a major challenge. Thus interception/prevention remains a preferable approach for OSCC management and control. In previous preclinical studies, we and others demonstrated the protective effects of black raspberry (BRB) against carcinogen-induced DNA damage and OSCC. Thus, to translate preclinical findings, we tested the hypothesis in a Phase 0 clinical study that BRB administration reduces DNA damage induced by B[a]P in the buccal cells of smokers. After enrolling 27 smokers, baseline buccal cells were collected before the administration of BRB lozenges (5/day for 8 weeks, 1 gm BRB powder/lozenge) at baseline, at the middle and the end of BRB administration. The last samples were collected 4 weeks after BRB cessation (washout period). B[a]P-induced DNA damage (BPDE-N2-dG) was evaluated by LC-MS/MS. BRB administration resulted in a significant reduction in DNA damage: 26.3% at the midpoint (P = .01506) compared to baseline, 36.1% at the end of BRB administration (P = .00355), and 16.6% after BRB cessation (P = .007586). Our results suggest the potential benefits of BRB as a chemopreventive agent against the development of TS-initiated OSCC.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Systematic assessment of serum i-tRF-AsnGTT in gastric cancer: a potential clinical biomarker. 胃癌血清 i-tRF-AsnGTT 系统评估：一种潜在的临床生物标记物

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae044

Xiaodan Jiang, Xun Li, Yang Li, Yu Zhang, Xinliang Gu, Wei Zong, Xianjuan Shen, Shaoqing Ju

{"title":"Systematic assessment of serum i-tRF-AsnGTT in gastric cancer: a potential clinical biomarker.","authors":"Xiaodan Jiang, Xun Li, Yang Li, Yu Zhang, Xinliang Gu, Wei Zong, Xianjuan Shen, Shaoqing Ju","doi":"10.1093/carcin/bgae044","DOIUrl":"10.1093/carcin/bgae044","url":null,"abstract":"Since gastric cancer (GC) shows no apparent signs in its early stages, most patients are diagnosed later with a poor prognosis. We therefore seek more sensitive and specific GC biomarkers. Small RNAs formed from tRNAs represent a novel class of non-coding RNAs that are highly abundant in bodily fluids and essential to biological metabolism. This study explores the potential of i-tRF-AsnGTT in gastric cancer diagnostics. To begin with, we sequenced i-tRF-AsnGTT using high-throughput methods. i-tRF-AsnGTT expression levels in GC were determined using real-time fluorescence polymerase chain reaction. Agarose gel electrophoresis, Sanger sequencing, and repeated freezing and thawing were performed to verify molecular properties. A correlation was found between clinical and pathological parameters and i-tRF-AsnGTT expression levels through the χ2 test, and receiver operating characteristic was used to analyze its diagnostic value in GC. In serum, i-tRF-AsnGTT has a low and stable expression level. It can differentiate between patients with gastric cancer and gastritis and healthy donors with better diagnostic efficacy. In combination with clinicopathological parameters, i-tRF-AsnGTT correlates with tumor differentiation; infiltration depth of tumors; tumor, node, metastasis stage; lymph node metastases; and neural/vascular invasion. Serum i-tRF-AsnGTT expression is low in GC patients. Serum from postoperative patients shows increased i-tRF-AsnGTT expression levels. Potentially, this could be used as a biomarker to help diagnose gastric cancer and monitor its prognosis.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 phospholipase D1 reduces pancreatic carcinogenesis in mice partly through a FAK-dependent mechanism. 抑制磷脂酶 D1 可部分通过 FAK 依赖性机制减少小鼠胰腺癌的发生。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae071

Hala A Addassi, Irena Krga, Fernando Villarreal, Joseph F LaComb, Michael A Frohman, Karen Matsukuma, Gerardo G Mackenzie

{"title":"Inhibition of phospholipase D1 reduces pancreatic carcinogenesis in mice partly through a FAK-dependent mechanism.","authors":"Hala A Addassi, Irena Krga, Fernando Villarreal, Joseph F LaComb, Michael A Frohman, Karen Matsukuma, Gerardo G Mackenzie","doi":"10.1093/carcin/bgae071","DOIUrl":"10.1093/carcin/bgae071","url":null,"abstract":"Phospholipase D (PLD) plays a critical role in cancer progression. However, its role in pancreatic cancer remains unclear. Thus, we evaluated the role of PLD1, one of two classical isoforms of PLD, in pancreatic carcinogenesis in vivo. The role of PLD1 in tumor growth was evaluated by subcutaneously transplanting human MIA PaCa-2 cells expressing endogenous PLD1 levels (Ctr KD cells) or cells in which PLD1 was knocked down (Pld1 KD cells) into immunodeficient mice. Twenty days post-implantation, tumors that arose from Pld1-KD cells were significantly smaller, compared to controls (Ctr KD). Then, we assessed the role of PLD1 in the tumor microenvironment, by subcutaneously implanting mouse LSL-KrasG12D/+;Trp53R172H/+;Pdx-1-Cre (KPC) cells into wild-type or PLD1 knockout (Pld1-/-) mice. Compared to wild type, tumor growth was attenuated in Pld1-/- mice by 39%, whereas treatment of Pld1-/- mice with gemcitabine reduced tumor growth by 79%. When PLD1 was ablated in LSL-KrasG12D;Ptf1Cre/+ (KC) mice, no reduction in acinar cell loss was observed, compared to KC mice. Finally, treatment of KC mice with a small molecule inhibitor of PLD1 and PLD2 (FIPI) significantly reduced acinar cell loss and cell proliferation, compared to vehicle-treated mice. Mechanistically, the effect of PLD on tumor growth is mediated, partly, by the focal adhesion kinase pathway. In conclusion, while PLD1 is a critical regulator of pancreatic xenograft and allograft growth, playing an important role at the tumor and at the microenvironment levels, the inhibition of PLD1 and PLD2 is necessary to reduce pancreatic carcinogenesis in KC mice and might represent a novel therapeutic target.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Advanced glycation end products promote the progression of endometrial cancer via activating the RAGE/CHKA/PI3K/AKT signaling pathway. 高级糖化终末产物通过激活 RAGE/CHKA/PI3K/AKT 信号通路促进子宫内膜癌的进展。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae059

Wan Shu, Teng Hua, Xiaoyan Xin, Jun Zhang, Jing Lin, Rui Shi, Rong Zhao, Wei Zhang, Ke-Jun Dong, Hongbo Wang, Xing Zhou

{"title":"Advanced glycation end products promote the progression of endometrial cancer via activating the RAGE/CHKA/PI3K/AKT signaling pathway.","authors":"Wan Shu, Teng Hua, Xiaoyan Xin, Jun Zhang, Jing Lin, Rui Shi, Rong Zhao, Wei Zhang, Ke-Jun Dong, Hongbo Wang, Xing Zhou","doi":"10.1093/carcin/bgae059","DOIUrl":"10.1093/carcin/bgae059","url":null,"abstract":"Endometrial cancer (EC) is a common malignant tumor that is closely associated with metabolic disorders such as diabetes and obesity. Advanced glycation end products (AGEs) are complex polymers formed by the reaction of reducing sugars with the amino groups of biomacromolecules, mediating the occurrence and development of many chronic metabolic diseases. Recent research has demonstrated that the accumulation of AGEs can affect the tumor microenvironment, metabolism, and signaling pathways, thereby affecting the malignant progression of tumors. However, the mechanism by which AGEs affect EC is unclear. Our research aimed to investigate how AGEs promote the development of EC through metabolic pathways and to explore their potential underlying mechanisms. Our experimental results demonstrated that AGEs upregulated the choline metabolism mediated by choline kinase alpha (CHKA) through the receptor for advanced glycation end products, activating the PI3K/AKT pathway and enhancing the malignant biological behavior of EC cells. Virtual screening and molecular dynamics simulation revealed that timosaponin A3 could target CHKA to inhibit AGE-induced progression of EC and that a newly discovered CHKA inhibitor could be a novel targeted inhibitor for the treatment of EC. This study provides new therapeutic strategies and contributes to the treatment of EC.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Ubiquitin-specific peptidase 49 promotes adenocarcinoma of the esophagogastric junction malignant progression via activating SHCBP1-β-catenin-GPX4 axis. USP49 通过激活 SHCBP1-β-catenin-GPX4 轴促进食管胃交界处腺癌的恶性发展。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2025-01-20 DOI: 10.1093/carcin/bgae060

Yun Ding, Zhen Liu, Xiaofeng Dai, Ruiwen Ruan, Hongguang Zhong, Zhipeng Wu, Yangyang Yao, Jun Chen, Jun Deng, Jianping Xiong

{"title":"Ubiquitin-specific peptidase 49 promotes adenocarcinoma of the esophagogastric junction malignant progression via activating SHCBP1-β-catenin-GPX4 axis.","authors":"Yun Ding, Zhen Liu, Xiaofeng Dai, Ruiwen Ruan, Hongguang Zhong, Zhipeng Wu, Yangyang Yao, Jun Chen, Jun Deng, Jianping Xiong","doi":"10.1093/carcin/bgae060","DOIUrl":"10.1093/carcin/bgae060","url":null,"abstract":"Adenocarcinoma of the esophagogastric junction (AEG) has received widespread attention because of its increasing incidence. However, the molecular mechanism underlying tumor progression remains unclear. Here, we report that the downregulation of ubiquitin-specific peptidase 49 (USP49) promotes ferroptosis in OE33 and OE19 cells, thereby inhibiting cell proliferation in vitro and in vivo, whereas the overexpression of USP49 had the opposite effect. In addition, USP49 downregulation promoted AEG cell radiotherapy sensitivity. Moreover, overexpression of Glutathione PeroXidase 4 reversed the ferroptosis and proliferation inhibition induced by USP49 knockdown. Mechanistically, USP49 deubiquitinates and stabilizes Shc SH2-domain-binding protein 1, subsequently facilitating the entry of β-catenin into the nucleus to enhance Glutathione PeroXidase 4 transcriptional expression. Finally, high USP49 expression was correlated with shorter overall survival in patients with AEG. In summary, our findings identify USP49 as a novel regulator of ferroptosis in AEG cells, indicating that USP49 may be a potential therapeutic target in AEG.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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