Molecular Carcinogenesis最新文献_第6页

Silmitasertib in Combination With Cabozantinib Impairs Liver Cancer Cell Cycle Progression, Induces Apoptosis, and Delays Tumor Growth in a Preclinical Model. 在临床前模型中，Silmitasertib与Cabozantinib联用可抑制肝癌细胞周期进展、诱导细胞凋亡并延缓肿瘤生长。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2024-10-08 DOI: 10.1002/mc.23827

Yuki Haga, Ranjit Ray, Ratna B Ray

{"title":"Silmitasertib in Combination With Cabozantinib Impairs Liver Cancer Cell Cycle Progression, Induces Apoptosis, and Delays Tumor Growth in a Preclinical Model.","authors":"Yuki Haga, Ranjit Ray, Ratna B Ray","doi":"10.1002/mc.23827","DOIUrl":"https://doi.org/10.1002/mc.23827","url":null,"abstract":"The rising incidence of hepatocellular carcinoma (HCC) is a global problem. Several approved treatments, including immune therapy and multi-tyrosine kinase inhibitors, are used for treatment, although the results are not optimum. There is an unmet need to develop highly effective chemotherapies for HCC. Targeting multiple pathways to attack cancer cells is beneficial. Cabozantinib is an orally available bioactive multikinase inhibitor and has a modest effect on HCC treatment. Silmitasertib is an orally bioavailable, potent CK2 inhibitor with a direct role in DNA damage repair and is in clinical trials for other cancers. In this study, we planned to repurpose these existing drugs on HCC treatment. We observed a stronger antiproliferative effect of these two combined drugs on HCC cells generated from different etiologies as compared to the single treatment. Global RNA-seq analyses revealed a decrease in the expression of G2/M cell cycle transition genes in HCC cells following combination treatment, suggesting G2 phase cell arrest. We observed G2/M cell cycle phase arrest in HCC cells upon combination treatment compared to the single-treated or vehicle-treated control cells. The downregulation of CCNA2 and CDC25C following combination therapy further supported the observation. Subsequent analyses demonstrated that combination treatment inhibited 70 kDa ribosomal protein S6 kinase (p70S6K) phosphorylation, and increased Bim expression. Apoptosis of HCC cells were accompanied by increased poly (ADP-ribose) polymerase cleavage and caspase-9 activation. Next, we observed that a combination therapy significantly delayed the progression of HCC xenograft growth as compared to vehicle control. Together, our results suggested combining cabozantinib and silmitasertib would be a promising treatment option for HCC.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391976","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

AKAP95 regulates ubiquitination and degradation of cyclin Ds/Es, influencing the G1/S transition of lung cancer cells. AKAP95 可调节细胞周期蛋白 Ds/Es 的泛素化和降解，从而影响肺癌细胞的 G1/S 转换。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2024-10-01 Epub Date: 2024-06-24 DOI: 10.1002/mc.23781

Zifeng Deng, Liangding Dou, Zhen Luo, Rong Liu, Jinwen Zhang, Jing Wang, Dai Wang, DongBei Guo, Ran An, Youliang Yao, Guihua Qiu, Yongxing Zhang

引用次数: 0

Latrophilin-3 as a downstream effector of the androgen receptor induces urothelial tumorigenesis. Latrophilin-3作为雄激素受体的下游效应因子诱导尿道肿瘤发生。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2024-10-01 Epub Date: 2024-06-24 DOI: 10.1002/mc.23783

Takuro Goto, Masato Yasui, Yuki Teramoto, Yujiro Nagata, Taichi Mizushima, Hiroshi Miyamoto

{"title":"Latrophilin-3 as a downstream effector of the androgen receptor induces urothelial tumorigenesis.","authors":"Takuro Goto, Masato Yasui, Yuki Teramoto, Yujiro Nagata, Taichi Mizushima, Hiroshi Miyamoto","doi":"10.1002/mc.23783","DOIUrl":"10.1002/mc.23783","url":null,"abstract":"Emerging evidence indicates that androgen receptor (AR) signaling plays a critical role in the pathogenesis of male-dominant urothelial cancer. Meanwhile, latrophilins (LPHNs), a group of the G-protein-coupled receptor to which a spider venom latrotoxin is known to bind, remain largely uncharacterized in neoplastic diseases. The present study aimed to determine the functional role of LPHN3 (encoded by the ADGRL3 gene), in association with AR signaling, in urothelial tumorigenesis. In human normal urothelial SVHUC cells, AR overexpression and androgen treatment considerably increased the expression levels of ADGRL3/LPHN3, while chromatin immunoprecipitation assay revealed the binding of AR to the promoter region of ADGRL3. In SVHUC or SVHUC-AR cells with exposure to a chemical carcinogen 3-methylcholanthrene, LPHN3 activation via ligand (e.g., α-latrotoxin, FLRT3) treatment during the process of the neoplastic/malignant transformation or LPHN3 knockdown via shRNA virus infection induced or reduced, respectively, the oncogenic activity. In N-butyl-N-(4-hydroxybutyl)nitrosamine-treated female mice, α-latrotoxin or FLRT3 injection accelerated the development of bladder tumors. Immunohistochemistry in surgical specimens further showed the significantly elevated expression of LPHN3 in non-muscle-invasive bladder tumors, compared with adjacent normal urothelial tissues, which was associated with a marginally (p = 0.051) higher risk of disease recurrence after transurethral resection. In addition, positivity of LPHN3 and AR in these tumors was strongly correlated. These findings indicate that LPHN3 functions as a downstream effector of AR and promotes urothelial tumorigenesis.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1847-1854"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458120","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

UBE2D1 promotes glioblastoma proliferation by modulating p21 ubiquitination. UBE2D1 通过调节 p21 泛素化促进胶质母细胞瘤增殖。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2024-10-01 Epub Date: 2024-07-17 DOI: 10.1002/mc.23786

Yongfeng Wang, Qianquan Ma, Haoyu Li, Wei Huang, Jia You, Dian Liu

引用次数: 0

Methylation, Gene Expression, and Risk Genotypes at the TERT-CLPTM1L Locus in Cervical Cancer. 宫颈癌中 TERT-CLPTM1L 基因座的甲基化、基因表达和风险基因型。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2024-10-01 DOI: 10.1002/mc.23822

Dhanya Ramachandran, Qianqian Mao, Dandan Liao, Maud Kamal, Peter Schürmann, Rieke Eisenblätter, Robert Geffers, Balazs Balint, Lolita Lecompte, Nicolas Servant, Linda Larbi Chérif, Constance Lamy, Sylvain Baulande, Patricia Legoix, Christophe Le Tourneau, Aurélien Latouche, Peter Hillemanns, Suzy Scholl, Thilo Dörk

{"title":"Methylation, Gene Expression, and Risk Genotypes at the TERT-CLPTM1L Locus in Cervical Cancer.","authors":"Dhanya Ramachandran, Qianqian Mao, Dandan Liao, Maud Kamal, Peter Schürmann, Rieke Eisenblätter, Robert Geffers, Balazs Balint, Lolita Lecompte, Nicolas Servant, Linda Larbi Chérif, Constance Lamy, Sylvain Baulande, Patricia Legoix, Christophe Le Tourneau, Aurélien Latouche, Peter Hillemanns, Suzy Scholl, Thilo Dörk","doi":"10.1002/mc.23822","DOIUrl":"10.1002/mc.23822","url":null,"abstract":"The reverse transcriptase subunit of telomerase, TERT, is frequently activated in high-grade dysplasia and invasive cancers of the uterine cervix. Telomerase activation through hypomethylation of the TERT promoter holds promise as a biomarker for cervical cancer progression, however, specific CpG sites involved in cervical cancer risk remain to be fully defined. A recent genome-wide association study on cervical cancer identified genetic polymorphisms at 5p13.33 (close to TERT-CLPTM1L) but the underlying mechanisms are undetermined. We investigated 529 CpG sites within the TERT promoter region and 3 CpG islands nearby, and 21 CpG sites within CLPTM1L in 190 bisulfite-converted cervical tumor DNA samples from BioRAIDs (NCT02428842). We identified eight CpG sites within TERT intron 2 where methylation was significantly associated with the genotypes of cervical cancer risk variants rs27070 and rs459961 in cervical tumors after multiple testing correction (p < 9.4 × 10E-5). Hypermethylation at chr5:1289663 correlated with decreased TERT mRNA levels. In an independent series of 188 normal or dysplastic cervical tissues, rare alleles of rs27070 and rs459961 were associated with low basal CLPTM1L levels and with the absence of TERT mRNA in HPV-negative samples, consistent with their proposed role as protective variants for cervical cancer. HPV infection was associated with increased CLPTM1L and TERT levels. Collectively, our results provide a link between cervical cancer risk variants, methylation, and gene expression and implicate both TERT and CLPTM1L as genes modulated by genomic background and HPV infection during cervical cancer development.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350545","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

Frizzled 6 endows high-grade serous ovarian cancer with stem-like properties and chemoresistance. Frizzled 6赋予高级别浆液性卵巢癌干样特性和化疗抗性。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2024-10-01 Epub Date: 2024-08-12 DOI: 10.1002/mc.23789

Shaorong Chen, Guang Yang, Qirong Shi, Ningning Wan, Ruyin Lin, Lianhua Wang, Xinxin Hu, Xuanxuan Zhuang, Liying Yu, Ming Sui

引用次数: 0

YAP-LAMB3 axis dictates cellular resistance of pancreatic ductal adenocarcinoma cells to gemcitabine. YAP-LAMB3 轴决定了胰腺导管腺癌细胞对吉西他滨的耐药性。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2024-10-01 Epub Date: 2024-07-17 DOI: 10.1002/mc.23785

Yecheng Li, Xiaolong Wang, Hongpei Yu, Jinming Cao, Jiaming Xie, Jinhong Zhou, Zhenyu Feng, Wei Chen

{"title":"YAP-LAMB3 axis dictates cellular resistance of pancreatic ductal adenocarcinoma cells to gemcitabine.","authors":"Yecheng Li, Xiaolong Wang, Hongpei Yu, Jinming Cao, Jiaming Xie, Jinhong Zhou, Zhenyu Feng, Wei Chen","doi":"10.1002/mc.23785","DOIUrl":"10.1002/mc.23785","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors with poor prognosis and inadequate response to treatment, such as gemcitabine (Gem), the first-line chemotherapeutic drug. Understanding the molecular determinants that control drug resistance to Gem is critical to predict potentially responsive patients and improve the benefits of Gem therapy. Emerging evidence suggests that certain developmental pathways, such as Hippo signaling, are aberrated and play important roles in Gem resistance in cancers. Although Hippo signaling has been reported to play a role in chemoresistance in cancers, it has not been clarified which specific target gene(s) functionally mediates the effect. In the present study, we found that YAP serves as a potent barrier for the cellular sensitivity of PDAC cells to Gem. We then identified and characterized laminin subunit beta 3 (LAMB3) as a bona fide target of YAP-TEAD4 to amplify YAP signaling via a feedback loop. Such a YAP-LAMB3 axis is critical to induce epithelial-mesenchymal transition and mediate Gem resistance. Taken together, we uncovered that YAP-LAMB3 axis is an important regulator of Gem, thus providing potential therapeutic targets for overcoming Gem resistance in PDAC.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1953-1966"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627216","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

C5AR1-induced TLR1/2 pathway activation drives proliferation and metastasis in anaplastic thyroid cancer. C5AR1诱导的TLR1/2通路活化推动了无性甲状腺癌的增殖和转移。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2024-10-01 Epub Date: 2024-06-27 DOI: 10.1002/mc.23784

Bo Liu, Yueyao Sun, Tongyao Geng, Haobo Wang, Zhenyu Wu, Lei Xu, Miao Zhang, Xupeng Niu, Chenxu Zhao, Jin Shang, Fangjian Shang

{"title":"C5AR1-induced TLR1/2 pathway activation drives proliferation and metastasis in anaplastic thyroid cancer.","authors":"Bo Liu, Yueyao Sun, Tongyao Geng, Haobo Wang, Zhenyu Wu, Lei Xu, Miao Zhang, Xupeng Niu, Chenxu Zhao, Jin Shang, Fangjian Shang","doi":"10.1002/mc.23784","DOIUrl":"10.1002/mc.23784","url":null,"abstract":"This study aimed to elucidate the role and mechanisms of Complement C5a receptor 1 (C5AR1) in driving the malignant progression of anaplastic thyroid carcinoma (ATC). C5AR1 expression was assessed in ATC tissues and cell lines. Functional assays evaluated the effects of C5AR1 knockdown on the malignant features of ATC cells. The interaction between C5AR1 and miR-335-5p was confirmed using a luciferase reporter assay and Fluorescence in situ hybridization, and the impact of C5AR1 knockdown on the Toll-like receptor (TLR) 1/2 signaling pathway was examined. In vivo studies evaluated the effects of C5AR1 modulation on tumor growth and metastasis. C5AR1 levels were elevated in ATC tumor samples and associated with poor survival in ATC patients. C5AR1 knockdown impeded ATC cell proliferation, migration, and invasion in vitro. MiR-335-5p was identified as an upstream regulator of C5AR1, which negatively modulates C5AR1 expression. C5AR1 knockdown diminished TLR1, TLR2, and myeloid differentiation primary response 88 (MyD88) levels, while C5AR1 overexpression activated this pathway. Blocking TLR1/2 signaling abrogated the oncogenic effects of C5AR1 overexpression. C5AR1 silencing inhibited tumor growth and lung metastasis of ATC cells in nude mice. C5AR1 contributes to ATC tumorigenesis and metastasis by activating the TLR1/2 pathway, and is negatively regulated by miR-335-5p. Targeting the miR-335-5p/C5AR1/TLR1/2 axis represents a potential therapeutic strategy for ATC.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1938-1952"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458117","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

The role of immune checkpoint inhibitors: Variable number of tandem repeat (VNTR) polymorphism in the second exon of the P-selectin glycoprotein ligand-1 (PSGL-1) gene polymorphism in multiple myeloma. 免疫检查点抑制剂的作用：多发性骨髓瘤中P-选择素糖蛋白配体-1（PSGL-1）基因第二外显子多态性的串联重复变异数（VNTR）。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2024-10-01 Epub Date: 2024-07-02 DOI: 10.1002/mc.23787

Yasemin Oyaci, Mustafa Pehlivan, Sacide Pehlivan, Tahir Alper Cinli, Fatima Ceren Tuncel, Elif Ertas, Istemi Serin

{"title":"The role of immune checkpoint inhibitors: Variable number of tandem repeat (VNTR) polymorphism in the second exon of the P-selectin glycoprotein ligand-1 (PSGL-1) gene polymorphism in multiple myeloma.","authors":"Yasemin Oyaci, Mustafa Pehlivan, Sacide Pehlivan, Tahir Alper Cinli, Fatima Ceren Tuncel, Elif Ertas, Istemi Serin","doi":"10.1002/mc.23787","DOIUrl":"10.1002/mc.23787","url":null,"abstract":"Somatic mutations and polymorphisms may play a role in multiple myeloma (MM) susceptibility and survival. One of the immune checkpoint inhibitors is P-selectin glycoprotein ligand-1 (PSGL-1); the majority of tumor-infiltrating leukocytes express PSGL-1, causing T cell and immune inhibition via PSGL-1 mediator molecules. We aimed to investigate the effect of variable number of tandem repeat (VNTR) polymorphism in the second exon of the PSGL-1 gene on MM susceptibility, response to treatment and survival in our patient group. A total of 238 patients diagnosed with MM between January 2010 and January 2021 and 162 healthy individuals as a control group were included in this cross-sectional study. The genotypes of the VNTR polymorphism in the second exon of the PSGL-1 gene were statistically compared between patients and healthy controls; the statistically significant effects of the genotypes on response to first-line treatment and survival were examined. The AC genotype was significantly higher in healthy controls compared to patients diagnosed with MM (p < 0.001). The median PFS in patients with AA/AB/AC was 56 months, while it was 100 months in patients with BB/CC. The hazard ratio of 1.34 for PFS was found to be clinically significant and having the BB/CC genotype could provide a longer PFS compared to others, but it was not statistically significant due to the sample size. Our study results will shed light on new study plans in terms of immune checkpoint target therapies among conventional treatment preferences in MM.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1980-1987"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492652","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

ATP citrate lyase promotes the progression of hepatocellular carcinoma by activating the REGγ-proteasome pathway. ATP 柠檬酸溶解酶通过激活 REGγ 蛋白酶体途径促进肝细胞癌的进展。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2024-10-01 Epub Date: 2024-06-18 DOI: 10.1002/mc.23777

Qihong Cai, Honghua Zhu, Yile Dai, Qingqing Zhou, Qiyu Zhang, Qiandong Zhu

{"title":"ATP citrate lyase promotes the progression of hepatocellular carcinoma by activating the REGγ-proteasome pathway.","authors":"Qihong Cai, Honghua Zhu, Yile Dai, Qingqing Zhou, Qiyu Zhang, Qiandong Zhu","doi":"10.1002/mc.23777","DOIUrl":"10.1002/mc.23777","url":null,"abstract":"The search for novel tumor biomarkers and targets is of significant importance for the early clinical diagnosis and treatment of Hepatocellular Carcinoma (HCC). The mechanisms by which ATP citrate lyase (ACLY) promotes HCC progression remain unclear, and the connection between ACLY and REGγ has not been reported in the literature. In vitro, we will perform overexpression/knockdown of ACLY or overexpression/knockdown of REGγ to investigate the impact of ACLY on HCC cells and its underlying mechanisms. In vivo, we will establish mouse tumor models with overexpression/knockdown of ACLY or overexpression/knockdown of REGγ to study the effect of ACLY on mouse tumors and its mechanisms. Firstly, ACLY overexpression upregulated REGγ expression and activated the REGγ-proteasome pathway, leading to changes in the expression of downstream signaling pathway proteins. This promoted HCC cell proliferation, invasion, and migration in vitro, as well as tumor growth and metastasis in vivo. Secondly, ACLY overexpression increased acetyl-CoA production, upregulated the acetylation level of the REGγ promoter region histone H3K27ac, and subsequently induced REGγ expression. Lastly, enhanced acetylation of the REGγ promoter region histone H3K27ac resulted in upregulated REGγ expression, activation of the REGγ-proteasome pathway, changes in downstream signaling pathway protein expression, and promotion of HCC cell proliferation, invasion, and migration in vitro, as well as tumor growth and metastasis in vivo. Conversely, REGγ knockdown reversed these effects. ACLY and REGγ may serve as potential biomarkers and clinical therapeutic targets for HCC.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1874-1891"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419946","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