Molecular Oncology最新文献_第9页

The stress sensor GCN2 differentially controls ribosome biogenesis in colon cancer according to the nutritional context. 应激传感器GCN2根据营养环境对结肠癌中核糖体生物发生的控制存在差异。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2024-09-01 Epub Date: 2023-08-18 DOI: 10.1002/1878-0261.13491

Marie Piecyk, Mouna Triki, Pierre-Alexandre Laval, Cedric Duret, Joelle Fauvre, Laura Cussonneau, Christelle Machon, Jerôme Guitton, Nicolas Rama, Benjamin Gibert, Gabriel Ichim, Frederic Catez, Fleur Bourdelais, Sebastien Durand, Jean-Jacques Diaz, Isabelle Coste, Toufic Renno, Serge N Manié, Nicolas Aznar, Stephane Ansieau, Carole Ferraro-Peyret, Cedric Chaveroux

{"title":"The stress sensor GCN2 differentially controls ribosome biogenesis in colon cancer according to the nutritional context.","authors":"Marie Piecyk, Mouna Triki, Pierre-Alexandre Laval, Cedric Duret, Joelle Fauvre, Laura Cussonneau, Christelle Machon, Jerôme Guitton, Nicolas Rama, Benjamin Gibert, Gabriel Ichim, Frederic Catez, Fleur Bourdelais, Sebastien Durand, Jean-Jacques Diaz, Isabelle Coste, Toufic Renno, Serge N Manié, Nicolas Aznar, Stephane Ansieau, Carole Ferraro-Peyret, Cedric Chaveroux","doi":"10.1002/1878-0261.13491","DOIUrl":"10.1002/1878-0261.13491","url":null,"abstract":"Nutrient availability is a key determinant of tumor cell behavior. While nutrient-rich conditions favor proliferation and tumor growth, scarcity, and particularly glutamine starvation, promotes cell dedifferentiation and chemoresistance. Here, linking ribosome biogenesis plasticity with tumor cell fate, we uncover that the amino acid sensor general control non-derepressible 2 (GCN2; also known as eIF-2-alpha kinase 4) represses the expression of the precursor of ribosomal RNA (rRNA), 47S, under metabolic stress. We show that blockade of GCN2 triggers cell death by an irremediable nucleolar stress and subsequent TP53-mediated apoptosis in patient-derived models of colon adenocarcinoma (COAD). In nutrient-rich conditions, a cell-autonomous GCN2 activity supports cell proliferation by stimulating 47S rRNA transcription, independently of the canonical integrated stress response (ISR) axis. Impairment of GCN2 activity prevents nuclear translocation of methionyl-tRNA synthetase (MetRS), resulting in nucleolar stress, mTORC1 inhibition and, ultimately, autophagy induction. Inhibition of the GCN2-MetRS axis drastically improves the cytotoxicity of RNA polymerase I (RNA pol I) inhibitors, including the first-line chemotherapy oxaliplatin, on patient-derived COAD tumoroids. Our data thus reveal that GCN2 differentially controls ribosome biogenesis according to the nutritional context. Furthermore, pharmacological co-inhibition of the two GCN2 branches and RNA pol I activity may represent a valuable strategy for elimination of proliferative and metabolically stressed COAD cells.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2111-2135"},"PeriodicalIF":6.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10022507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

The CK1ε/SIAH1 axis regulates AXIN1 stability in colorectal cancer cells. CK1ε/SIAH1 轴调节结直肠癌细胞中 AXIN1 的稳定性。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2024-09-01 Epub Date: 2024-02-28 DOI: 10.1002/1878-0261.13624

Mengfang Yan, Zijie Su, Xiaoyi Pang, Hanbin Wang, Han Dai, Jiong Ning, Shanshan Liu, Qi Sun, Jiaxing Song, Xibao Zhao, Desheng Lu

{"title":"The CK1ε/SIAH1 axis regulates AXIN1 stability in colorectal cancer cells.","authors":"Mengfang Yan, Zijie Su, Xiaoyi Pang, Hanbin Wang, Han Dai, Jiong Ning, Shanshan Liu, Qi Sun, Jiaxing Song, Xibao Zhao, Desheng Lu","doi":"10.1002/1878-0261.13624","DOIUrl":"10.1002/1878-0261.13624","url":null,"abstract":"Casein kinase 1ε (CK1ε) and axis inhibitor 1 (AXIN1) are crucial components of the β-catenin destruction complex in canonical Wnt signaling. CK1ε has been shown to interact with AXIN1, but its physiological function and role in tumorigenesis remain unknown. In this study, we found that CK1δ/ε inhibitors significantly enhanced AXIN1 protein level in colorectal cancer (CRC) cells through targeting CK1ε. Mechanistically, CK1ε promoted AXIN1 degradation by the ubiquitin-proteasome pathway by promoting the interaction of E3 ubiquitin-protein ligase SIAH1 with AXIN1. Genetic or pharmacological inhibition of CK1ε and knockdown of SIAH1 downregulated the expression of Wnt/β-catenin-dependent genes, suppressed the viability of CRC cells, and restrained tumorigenesis and progression of CRC in vitro and in vivo. In summary, our results demonstrate that CK1ε exerted its oncogenic role in CRC occurrence and progression by regulating the stability of AXIN1. These findings reveal a novel mechanism by which CK1ε regulates the Wnt/β-catenin signaling pathway and highlight the therapeutic potential of targeting the CK1ε/SIAH1 axis in CRC.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2277-2297"},"PeriodicalIF":6.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

The MYC-NFATC2 axis maintains the cell cycle and mitochondrial function in acute myeloid leukaemia cells. MYC-NFATC2 轴可维持急性髓性白血病细胞的细胞周期和线粒体功能。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2024-09-01 Epub Date: 2024-03-08 DOI: 10.1002/1878-0261.13630

Shaun D Patterson, Matthew E Massett, Xu Huang, Heather G Jørgensen, Alison M Michie

{"title":"The MYC-NFATC2 axis maintains the cell cycle and mitochondrial function in acute myeloid leukaemia cells.","authors":"Shaun D Patterson, Matthew E Massett, Xu Huang, Heather G Jørgensen, Alison M Michie","doi":"10.1002/1878-0261.13630","DOIUrl":"10.1002/1878-0261.13630","url":null,"abstract":"Acute myeloid leukaemia (AML) is a clonal haematological malignancy affecting the myeloid lineage, with generally poor patient outcomes owing to the lack of targeted therapies. The histone lysine demethylase 4A (KDM4A) has been established as a novel therapeutic target in AML, due to its selective oncogenic role within leukaemic cells. We identify that the transcription factor nuclear factor of activated T cells 2 (NFATC2) is a novel binding and transcriptional target of KDM4A in the human AML THP-1 cell line. Furthermore, cytogenetically diverse AML cell lines, including THP-1, were dependent on NFATC2 for colony formation in vitro, highlighting a putative novel mechanism of AML oncogenesis. Our study demonstrates that NFATC2 maintenance of cell cycle progression in human AML cells was driven primarily by CCND1. Through RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq), NFATc2 was shown to bind to the promoter region of genes involved in oxidative phosphorylation and subsequently regulate their gene expression in THP-1 cells. Furthermore, our data show that NFATC2 shares transcriptional targets with the transcription factor c-MYC, with MYC knockdown phenocopying NFATC2 knockdown. These data suggest a newly identified co-ordinated role for NFATC2 and MYC in the maintenance of THP-1 cell function, indicative of a potential means of therapeutic targeting in human AML.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2234-2254"},"PeriodicalIF":6.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140065507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Hyaluronic acid metabolism and chemotherapy resistance: recent advances and therapeutic potential. 透明质酸代谢和化疗耐药:最新进展和治疗潜力。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2024-09-01 Epub Date: 2024-03-21 DOI: 10.1002/1878-0261.13551

Zhanhong Liu, Pengbo Hou, Jiankai Fang, Changshun Shao, Yufang Shi, Gerry Melino, Angelo Peschiaroli

引用次数: 0

Acetylated KHSRP impairs DNA-damage-response-related mRNA decay and facilitates prostate cancer tumorigenesis. 乙酰化的 KHSRP 会影响 DNA 损伤反应相关 mRNA 的衰变，并促进前列腺癌的发生。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2024-09-01 Epub Date: 2024-03-19 DOI: 10.1002/1878-0261.13634

Haihua Yuan, Renjie Cai, Biying Chen, Qian Wang, Mengting Wang, Junyi An, Weishu An, Ye Tao, Jianxiu Yu, Bin Jiang, Yanjie Zhang, Ming Xu

{"title":"Acetylated KHSRP impairs DNA-damage-response-related mRNA decay and facilitates prostate cancer tumorigenesis.","authors":"Haihua Yuan, Renjie Cai, Biying Chen, Qian Wang, Mengting Wang, Junyi An, Weishu An, Ye Tao, Jianxiu Yu, Bin Jiang, Yanjie Zhang, Ming Xu","doi":"10.1002/1878-0261.13634","DOIUrl":"10.1002/1878-0261.13634","url":null,"abstract":"Androgen-regulated DNA damage response (DDR) is one of the essential mechanisms in prostate cancer (PCa), a hormone-sensitive disease. The heterogeneous nuclear ribonucleoprotein K (hnRNPK)-homology splicing regulatory protein known as far upstream element-binding protein 2 (KHSRP) is an RNA-binding protein that can attach to AU-rich elements in the 3' untranslated region (3'-UTR) of messenger RNAs (mRNAs) to mediate mRNA decay and emerges as a critical regulator in the DDR to preserve genome integrity. Nevertheless, how KHSRP responds to androgen-regulated DDR in PCa development remains unclear. This study found that androgen can significantly induce acetylation of KHSRP, which intrinsically drives tumor growth in xenografted mice. Moreover, enhanced KHSRP acetylation upon androgen stimuli impedes KHSRP-regulated DDR gene expression, as seen by analyzing RNA sequencing (RNA-seq) and Gene Set Enrichment Analysis (GSEA) datasets. Additionally, NAD-dependent protein deacetylase sirtuin-7 (SIRT7) is a promising deacetylase of KHSRP, and androgen stimuli impairs its interaction with KHSRP to sustain the increased KHSRP acetylation level in PCa. We first report the acetylation of KHSRP induced by androgen, which interrupts the KHSRP-regulated mRNA decay of the DDR-related genes to promote the tumorigenesis of PCa. This study provides insight into KHSRP biology and potential therapeutic strategies for PCa treatment, particularly that of castration-resistant PCa.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2314-2330"},"PeriodicalIF":6.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140158528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Vitamin-C-dependent downregulation of the citrate metabolism pathway potentiates pancreatic ductal adenocarcinoma growth arrest. 依赖于维生素 C 的柠檬酸盐代谢途径下调可促进胰腺导管腺癌生长停滞。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2024-09-01 Epub Date: 2024-02-29 DOI: 10.1002/1878-0261.13616

Aiora Cenigaonandia-Campillo, Ana Garcia-Bautista, Anxo Rio-Vilariño, Arancha Cebrian, Laura Del Puerto, José Antonio Pellicer, José Antonio Gabaldón, Horacio Pérez-Sánchez, Miguel Carmena-Bargueño, Carolina Meroño, Javier Traba, María Jesús Fernandez-Aceñero, Natalia Baños-Herraiz, Lorena Mozas-Vivar, Estrella Núñez-Delicado, Jesús Garcia-Foncillas, Óscar Aguilera

{"title":"Vitamin-C-dependent downregulation of the citrate metabolism pathway potentiates pancreatic ductal adenocarcinoma growth arrest.","authors":"Aiora Cenigaonandia-Campillo, Ana Garcia-Bautista, Anxo Rio-Vilariño, Arancha Cebrian, Laura Del Puerto, José Antonio Pellicer, José Antonio Gabaldón, Horacio Pérez-Sánchez, Miguel Carmena-Bargueño, Carolina Meroño, Javier Traba, María Jesús Fernandez-Aceñero, Natalia Baños-Herraiz, Lorena Mozas-Vivar, Estrella Núñez-Delicado, Jesús Garcia-Foncillas, Óscar Aguilera","doi":"10.1002/1878-0261.13616","DOIUrl":"10.1002/1878-0261.13616","url":null,"abstract":"In pancreatic ductal adenocarcinoma (PDAC), metabolic rewiring and resistance to standard therapy are closely associated. PDAC cells show enormous requirements for glucose-derived citrate, the first rate-limiting metabolite in the synthesis of new lipids. Both the expression and activity of citrate synthase (CS) are extraordinarily upregulated in PDAC. However, no previous relationship between gemcitabine response and citrate metabolism has been documented in pancreatic cancer. Here, we report for the first time that pharmacological doses of vitamin C are capable of exerting an inhibitory action on the activity of CS, reducing glucose-derived citrate levels. Moreover, ascorbate targets citrate metabolism towards the de novo lipogenesis pathway, impairing fatty acid synthase (FASN) and ATP citrate lyase (ACLY) expression. Lowered citrate availability was found to be directly associated with diminished proliferation and, remarkably, enhanced gemcitabine response. Moreover, the deregulated citrate-derived lipogenic pathway correlated with a remarkable decrease in extracellular pH through inhibition of lactate dehydrogenase (LDH) and overall reduced glycolytic metabolism. Modulation of citric acid metabolism in highly chemoresistant pancreatic adenocarcinoma, through molecules such as vitamin C, could be considered as a future clinical option to improve patient response to standard chemotherapy regimens.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2212-2233"},"PeriodicalIF":6.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

The selenoenzyme type I iodothyronine deiodinase: a new tumor suppressor in ovarian cancer. 硒酶Ⅰ型碘甲状腺原氨酸脱碘酶：卵巢癌中一种新的肿瘤抑制因子。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2024-09-01 Epub Date: 2024-03-01 DOI: 10.1002/1878-0261.13612

Adi Alfandari, Dotan Moskovich, Avivit Weisz, Aviva Katzav, Debora Kidron, Mario Beiner, Dana Josephy, Aula Asali, Yael Hants, Yael Yagur, Omer Weitzner, Martin Ellis, Gilad Itchaki, Osnat Ashur-Fabian

{"title":"The selenoenzyme type I iodothyronine deiodinase: a new tumor suppressor in ovarian cancer.","authors":"Adi Alfandari, Dotan Moskovich, Avivit Weisz, Aviva Katzav, Debora Kidron, Mario Beiner, Dana Josephy, Aula Asali, Yael Hants, Yael Yagur, Omer Weitzner, Martin Ellis, Gilad Itchaki, Osnat Ashur-Fabian","doi":"10.1002/1878-0261.13612","DOIUrl":"10.1002/1878-0261.13612","url":null,"abstract":"The selenoenzyme type I iodothyronine deiodinase (DIO1) catalyzes removal of iodine atoms from thyroid hormones. Although DIO1 action is reported to be disturbed in several malignancies, no work has been conducted in high-grade serous ovarian carcinoma (HGSOC), the most lethal gynecologic cancer. We studied DIO1 expression in HGSOC patients [The Cancer Genome Atlas (TCGA) data and tumor tissues], human cell lines (ES-2 and Kuramochi), normal Chinese hamster ovarian cells (CHO-K1), and normal human fallopian tube cells (FT282 and FT109). To study its functional role, DIO1 was overexpressed, inhibited [by propylthiouracil (PTU)], or knocked down (KD), and cell count, proliferation, apoptosis, cell viability, and proteomics analysis were performed. Lower DIO1 levels were observed in HGSOC compared to normal cells and tissues. TCGA analyses confirmed that low DIO1 mRNA expression correlated with worse survival and therapy resistance in patients. Silencing or inhibiting the enzyme led to enhanced ovarian cancer proliferation, while an opposite effect was shown following DIO1 ectopic expression. Proteomics analysis in DIO1-KD cells revealed global changes in proteins that facilitate tumor metabolism and progression. In conclusion, DIO1 expression and ovarian cancer progression are inversely correlated, highlighting a tumor suppressive role for this enzyme and its potential use as a biomarker in this disease.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2298-2313"},"PeriodicalIF":6.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

KRAS and GNAS mutations in cell-free DNA and in circulating epithelial cells in patients with intraductal papillary mucinous neoplasms-an observational pilot study. 导管内乳头状黏液性肿瘤患者无细胞DNA和循环上皮细胞中的KRAS和GNAS突变--一项观察性试验研究。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2024-09-01 DOI: 10.1002/1878-0261.13719

Christine Nitschke, Marie Tölle, Philipp Walter, Kira Meißner, Mara Goetz, Jolanthe Kropidlowski, Andreas W Berger, Jakob R Izbicki, Felix Nickel, Thilo Hackert, Klaus Pantel, Harriet Wikman, Faik G Uzunoglu

{"title":"KRAS and GNAS mutations in cell-free DNA and in circulating epithelial cells in patients with intraductal papillary mucinous neoplasms-an observational pilot study.","authors":"Christine Nitschke, Marie Tölle, Philipp Walter, Kira Meißner, Mara Goetz, Jolanthe Kropidlowski, Andreas W Berger, Jakob R Izbicki, Felix Nickel, Thilo Hackert, Klaus Pantel, Harriet Wikman, Faik G Uzunoglu","doi":"10.1002/1878-0261.13719","DOIUrl":"https://doi.org/10.1002/1878-0261.13719","url":null,"abstract":"Intraductal papillary mucinous neoplasms (IPMNs) are potential precursor lesions of pancreatic cancer. We assessed the efficacy of screening for KRAS proto-oncogene, GTPase (KRAS), and GNAS complex locus (GNAS) mutations in cell-free DNA (cfDNA)-using digital droplet polymerase chain reaction (ddPCR) and circulating epithelial cell (CEC) detection-as biomarkers for risk stratification in IPMN patients. We prospectively collected plasma samples from 25 resected patients at risk of malignant progression, and 23 under clinical surveillance. Our findings revealed KRAS mutations in 10.4% and GNAS mutations in 18.8% of the overall cohort. Among resected IPMN patients, KRAS and GNAS mutation detection rates were 16.0% and 32.0%, respectively, whereas both rates were 4.0% in conservatively managed IPMN. GNAS mutations in cfDNA were significantly more prevalent in resected IPMN (P = 0.024) compared with IPMN under surveillance. No CECs were detected. The absence of KRAS and GNAS mutations could be a reliable marker for branch duct IPMN without worrisome features. The emergence of GNAS mutations could prompt enhanced imaging surveillance. Neither the presence of established worrisome features nor GNAS or KRAS mutations appear effective in identifying high-grade dysplasia among IPMN patients.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109590","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

APOBEC3C-mediated NF-κB activation enhances clear cell renal cell carcinoma progression. APOBEC3C 介导的 NF-κB 激活可促进透明细胞肾细胞癌的进展。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2024-08-26 DOI: 10.1002/1878-0261.13721

Nora Hase, Danny Misiak, Helge Taubert, Stefan Hüttelmaier, Michael Gekle, Marcel Köhn

{"title":"APOBEC3C-mediated NF-κB activation enhances clear cell renal cell carcinoma progression.","authors":"Nora Hase, Danny Misiak, Helge Taubert, Stefan Hüttelmaier, Michael Gekle, Marcel Köhn","doi":"10.1002/1878-0261.13721","DOIUrl":"https://doi.org/10.1002/1878-0261.13721","url":null,"abstract":"Renowned as the predominant form of kidney cancer, clear cell renal cell carcinoma (ccRCC) exhibits susceptibility to immunotherapies due to its specific expression profile as well as notable immune cell infiltration. Despite this, effectively treating metastatic ccRCC remains a significant challenge, necessitating a more profound comprehension of the underlying molecular mechanisms governing its progression. Here, we unveil that the enhanced expression of the RNA-binding protein DNA dC → dU-editing enzyme APOBEC-3C (APOBEC3C; also known as A3C) in ccRCC tissue and ccRCC-derived cell lines serves as a catalyst for tumor growth by amplifying nuclear factor-kappa B (NF-κB) activity. By employing RNA-sequencing and cell-based assays in ccRCC-derived cell lines, we determined that A3C is a stress-responsive factor and crucial for cell survival. Furthermore, we identified that A3C binds and potentially stabilizes messenger RNAs (mRNAs) encoding positive regulators of the NF-κB pathway. Upon A3C depletion, essential subunits of the NF-κB family are abnormally restrained in the cytoplasm, leading to deregulation of NF-κB target genes. Our study illuminates the pivotal role of A3C in promoting ccRCC tumor development, positioning it as a prospective target for future therapeutic strategies.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056096","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

Unravelling the mosaic: Epigenetic diversity in glioblastoma. 揭开马赛克：胶质母细胞瘤的表观遗传多样性。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2024-08-15 DOI: 10.1002/1878-0261.13706

Sara Lucchini, Myrianni Constantinou, Silvia Marino

引用次数: 0