Carcinogenesis最新文献_第3页

PPP1r18 promotes tumor progression in esophageal squamous cell carcinoma by regulating the calcineurin-mediated ERK pathway. PPP1r18 通过调节钙神经蛋白介导的 ERK 通路促进食管鳞状细胞癌的肿瘤进展。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-09-11 DOI: 10.1093/carcin/bgae028

Changhao Ren, Linfeng Wu, Shaoyuan Zhang, Kangwei Qi, Yifei Zhang, Jiacheng Xu, Yuanyuan Ruan, Mingxiang Feng

{"title":"PPP1r18 promotes tumor progression in esophageal squamous cell carcinoma by regulating the calcineurin-mediated ERK pathway.","authors":"Changhao Ren, Linfeng Wu, Shaoyuan Zhang, Kangwei Qi, Yifei Zhang, Jiacheng Xu, Yuanyuan Ruan, Mingxiang Feng","doi":"10.1093/carcin/bgae028","DOIUrl":"10.1093/carcin/bgae028","url":null,"abstract":"Esophageal cancer is one of the most common malignant tumors, and the 5-year overall survival rate is only 20%. Esophageal squamous cell carcinoma (ESCC) is the primary histological type of esophageal carcinoma in China. Protein phosphatase 1 regulatory subunit 18 (PPP1r18) is one of the actin-regulatory proteins and is able to bind to protein phosphatase 1 catalytic subunit alpha (PPP1CA). Yet, little is known about the role of PPP1r18 in ESCC. This study aimed to elucidate the biological functions of PPP1r18 in the ESCC progression. Clinical samples first confirmed that PPP1r18 expression was upregulated in ESCC, and PPP1r18 was correlated with tumor invasion depth, lymph node metastasis, distant metastasis and reduced overall survival. We then observed that PPP1r18 overexpression enhanced cell proliferation in vitro and in vivo. Mechanistically, PPP1r18 regulated tumor progression of ESCC through activating the calcineurin-mediated ERK pathway, rather than binding to PPP1CA. Collectively, our results suggest that PPP1r18 promotes ESCC progression by regulating the calcineurin-mediated ERK pathway. PPP1r18 might be a potential target for the diagnosis and treatment of ESCC.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875954","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

Stem cells, Notch-1 signaling, and oxidative stress: a hellish trio in cancer development and progression within the airways. Is there a role for natural compounds? 干细胞、Notch-1 信号传导和氧化应激：气道内癌症发展和恶化的地狱三重奏。天然化合物能发挥作用吗？

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-09-11 DOI: 10.1093/carcin/bgae049

Giuseppina Chiappara, Serena Di Vincenzo, Caterina Cascio, Elisabetta Pace

引用次数: 0

USP49 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 : 2024-09-05 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":"USP49 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":"https://doi.org/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 (GPX4) reversed the ferroptosis and proliferation inhibition induced by USP49 knockdown. Mechanistically, USP49 deubiquitinates and stabilizes Shc SH2-domain binding protein 1 (SHCBP1), subsequently facilitating the entry of β-catenin into the nucleus to enhance GPX4 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":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-05","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

HuR/miR-124-3p/VDR complex bridges lipid metabolism and tumor development in colorectal cancer. HuR/miR-124-3p/VDR复合物是结直肠癌脂质代谢和肿瘤发生的桥梁。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-09-02 DOI: 10.1093/carcin/bgae061

Fengxing Huang, Luping Bu, Mengting Li, Youwei Wang, Runan Zhang, Yu Shao, Kun Lin, Hong Yang, Qiu Zhao, Lan Liu

{"title":"HuR/miR-124-3p/VDR complex bridges lipid metabolism and tumor development in colorectal cancer.","authors":"Fengxing Huang, Luping Bu, Mengting Li, Youwei Wang, Runan Zhang, Yu Shao, Kun Lin, Hong Yang, Qiu Zhao, Lan Liu","doi":"10.1093/carcin/bgae061","DOIUrl":"https://doi.org/10.1093/carcin/bgae061","url":null,"abstract":"Maintaining a balanced lipid status to prevent lipotoxicity is of paramount importance in various tumors, including colorectal cancer (CRC). HuR, an RNA-binding protein family member, exhibits high expression in many cancers possibly because it regulates cell proliferation, migration, invasion, and lipid metabolism. However, the role of HuR in the regulation of abnormal lipid metabolism in CRC remains unknown. We found that HuR promotes vitamin D receptor (VDR) expression to ensure lipid homeostasis by increasing Triglyceride (TG) and Total Cholesterol (TC) levels in CRC, thus confirming the direct binding of an overexpressed HuR to the CDS and 3'-UTR of Vdr, enhancing its expression. Concurrently, HuR can indirectly affect VDR expression by inhibiting miR-124-3p. HuR can suppress the expression of miR-124-3p, which binds to the 3'-UTR of Vdr, thereby reducing VDR expression. Additionally, a xenograft model demonstrated that targeting HuR inhibits VDR expression, blocking TG and TC formation, and hence mitigating CRC growth. Our findings suggest a regulatory relationship among HuR, miR-124-3p, and VDR in CRC. We propose that the HuR/miR-124-3p/VDR complex governs lipid homeostasis by impacting TG and TC formation in CRC, offering a potential therapeutic target for CRC prevention and treatment.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104642","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

The BAG3-IFITM2 Axis Enhances Pancreatic Ductal Adenocarcinoma Growth via the MAPK Signaling Pathway. BAG3-IFITM2 轴通过 MAPK 信号通路促进胰腺导管腺癌生长

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-08-30 DOI: 10.1093/carcin/bgae053

Peipei Wang, Congliang Chen, Kexin Lin, Yu Zhang, Junmei Hu, Tongbo Zhu, Xia Wang

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 : 2024-08-24 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":"https://doi.org/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 (RAGE), activating the PI3K/AKT pathway and enhancing the malignant biological behavior of EC cells. Virtual screening and molecular dynamics simulation revealed that timosaponin A3 (timo 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":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-24","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

ADRA2A promotes the classical/progenitor subtype and reduces disease aggressiveness of pancreatic cancer. ADRA2A 可促进胰腺癌的经典/祖细胞亚型并降低疾病的侵袭性。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-08-13 DOI: 10.1093/carcin/bgae056

Paloma Moreno, Yuuki Ohara, Amanda J Craig, Huaitian Liu, Shouhui Yang, Tiffany H Dorsey, Lin Zhang, Gatikrushna Panigrahi, Helen Cawley, Azadeh Azizian, Jochen Gaedcke, Michael Ghadimi, Nader Hanna, S Perwez Hussain

{"title":"ADRA2A promotes the classical/progenitor subtype and reduces disease aggressiveness of pancreatic cancer.","authors":"Paloma Moreno, Yuuki Ohara, Amanda J Craig, Huaitian Liu, Shouhui Yang, Tiffany H Dorsey, Lin Zhang, Gatikrushna Panigrahi, Helen Cawley, Azadeh Azizian, Jochen Gaedcke, Michael Ghadimi, Nader Hanna, S Perwez Hussain","doi":"10.1093/carcin/bgae056","DOIUrl":"10.1093/carcin/bgae056","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) manifests diverse molecular subtypes, including the classical/progenitor and basal-like/squamous subtypes, with the latter known for its aggressiveness. We employed integrative transcriptome and metabolome analyses to identify potential genes contributing to the molecular subtype differentiation and its metabolic features. Our comprehensive analysis revealed that adrenoceptor alpha 2A (ADRA2A) was downregulated in the basal-like/squamous subtype, suggesting its potential role as a candidate suppressor of this subtype. Reduced ADRA2A expression was significantly associated with a high frequency of lymph node metastasis, higher pathological grade, advanced disease stage, and decreased survival among PDAC patients. In vitro experiments demonstrated that ADRA2A transgene expression and ADRA2A agonist inhibited PDAC cell invasion. Additionally, ADRA2A-high condition downregulated the basal-like/squamous gene expression signature, while upregulating the classical/progenitor gene expression signature in our PDAC patient cohort and PDAC cell lines. Metabolome analysis conducted on the PDAC cohort and cell lines revealed that elevated ADRA2A levels were associated with suppressed amino acid and carnitine/acylcarnitine metabolism, which are characteristic metabolic profiles of the classical/progenitor subtype. Collectively, our findings suggest that heightened ADRA2A expression induces transcriptome and metabolome characteristics indicative of classical/progenitor subtype with decreased disease aggressiveness in PDAC patients. These observations introduce ADRA2A as a candidate for diagnostic and therapeutic targeting in PDAC.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970675","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

Sevoflurane inhibits lung cancer development by promoting FUS1 transcription via downregulating IRF6. 七氟烷通过下调IRF6促进FUS1转录，从而抑制肺癌发展

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-08-12 DOI: 10.1093/carcin/bgae034

Pei Zhou, Lei Yang, Xinyu Ma, Qiuguo Li

{"title":"Sevoflurane inhibits lung cancer development by promoting FUS1 transcription via downregulating IRF6.","authors":"Pei Zhou, Lei Yang, Xinyu Ma, Qiuguo Li","doi":"10.1093/carcin/bgae034","DOIUrl":"10.1093/carcin/bgae034","url":null,"abstract":"Lung cancer is a major contributor to cancer deaths worldwide and is on the rise. Although surgical resection has been widely used as a standard therapy for lung cancer patients, the relapse rate after surgery is high. It is still unclear whether there is a potential drug that can reduce the probability of postsurgical recurrence in lung cancer patients. We used 5 typical lung cancer cell lines as well as 41 lung cancer tissue samples and paracancer tissue samples to investigate the expression levels of interferon regulatory factor 6 (IRF6) and tumor suppressor candidate 2 (TUSC2, also known as FUS1). We also treated lung cancer cells (H322 and A549) with different concentrations of sevoflurane to study its influence on lung cancer cell tumorigenesis. Lentivirus-mediated gain-of-function studies of IRF6 and FUS1 were applied to validate the role of IRF6 and FUS1 in lung cancer. Next, we used short hairpin RNA-mediated loss of function of IRF6 and luciferase, chromatin immunoprecipitation assays to validate the regulatory role of IRF6 on FUS1. Our findings reported that IRF6 was upregulated in lung cancer tissues, while FUS1 was downregulated. Functional assays revealed that sevoflurane inhibits lung cancer development by downregulating IRF6 expression. Luciferase and chromatin immunoprecipitation-quantitative real-time PCR assays uncovered that IRF6 represses FUS1 transcriptional expression in lung cancer cells. We have shown that sevoflurane prevents lung cancer development by downregulating IRF6 to stimulate FUS1 transcription, indicating that sevoflurane can be used as the potential anesthetic drug in surgical resection to reduce postoperative tumor relapse in lung cancer patients.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178096","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

Diverse functions of Tribbles homolog 3 in cancers and its potential as a therapeutic target. TRIB3 在癌症中的多种功能及其作为治疗靶点的潜力。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-08-12 DOI: 10.1093/carcin/bgae042

Shiying Lei, Jiajun Sun, Yifang Xie, Xiaojuan Xiao, Xiaofeng He, Sheng Lin, Huifang Zhang, Zineng Huang, Haiqin Wang, Xusheng Wu, Hongling Peng, Jing Liu

{"title":"Diverse functions of Tribbles homolog 3 in cancers and its potential as a therapeutic target.","authors":"Shiying Lei, Jiajun Sun, Yifang Xie, Xiaojuan Xiao, Xiaofeng He, Sheng Lin, Huifang Zhang, Zineng Huang, Haiqin Wang, Xusheng Wu, Hongling Peng, Jing Liu","doi":"10.1093/carcin/bgae042","DOIUrl":"10.1093/carcin/bgae042","url":null,"abstract":"Currently, cancer is the second leading cause of death worldwide, and potential targeted drugs and molecular pathways for cancer development and progression have been a hot research topic worldwide. In recent years, the importance of the kinase superfamily in diseases has been well demonstrated by studies on various molecular mechanisms of kinases and the successful application of their inhibitors in diseases. Pseudokinases are members of the kinase superfamily, which have been increasingly documented to play a crucial role in cancers year after year. As a member of pseudokinases, tribbles homolog 3 (TRIB3) also exerts diverse functions in different cancers through different interacting proteins and molecular pathways, especially in tumor immunity, stemness, drug resistance, metabolism, and autophagy. In addition, peptide drugs targeting TRIB3 have high specificity in preclinical studies, which shows great promise for TRIB3 application in diseases including cancers. In this review, we dissect diverse functions played by TRIB3 in different cancers, describing the underlying mechanisms in detail. Notably, inhibitors and agonists currently available for TRIB3 are discussed, indicating the potential for TRIB3 as a therapeutic target.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431485","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

CacyBP promotes the development of lung adenocarcinoma by regulating OTUD5. CacyBP 通过调控 OTUD5 促进肺腺癌的发展。

IF 3.3 3区医学

Carcinogenesis Pub Date : 2024-08-12 DOI: 10.1093/carcin/bgae023

Mixue Bai, Kun Lu, Yingying Che, Lin Fu

{"title":"CacyBP promotes the development of lung adenocarcinoma by regulating OTUD5.","authors":"Mixue Bai, Kun Lu, Yingying Che, Lin Fu","doi":"10.1093/carcin/bgae023","DOIUrl":"10.1093/carcin/bgae023","url":null,"abstract":"Lung cancer is the most common and lethal malignancy, with lung adenocarcinoma accounting for approximately 40% of all cases. Despite some progress in understanding the pathogenesis of this disease and developing new therapeutic approaches, the current treatments for lung adenocarcinoma remain ineffective due to factors such as high tumour heterogeneity and drug resistance. Therefore, there is an urgent need to identify novel therapeutic targets. Calcyclin-binding protein (CacyBP) can regulate a variety of physiological processes by binding to different proteins, but its function in lung adenocarcinoma is unknown. Here, we show that CacyBP is highly expressed in lung adenocarcinoma tissues, and high CacyBP expression correlates with poorer patient survival. Moreover, overexpression of CacyBP promoted the proliferation, migration and invasion of lung adenocarcinoma cell lines. Further mechanistic studies revealed that CacyBP interacts with the tumour suppressor ovarian tumour (OTU) deubiquitinase 5 (OTUD5), enhances the ubiquitination and proteasomal degradation of OTUD5 and regulates tumourigenesis via OTUD5. In conclusion, our study reveals a novel mechanism by which CacyBP promotes tumourigenesis by increasing the ubiquitination level and proteasome-dependent degradation of OTUD5, providing a potential target for the treatment of lung adenocarcinoma.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334839","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