Oncogenesis最新文献_第6页

Acidovorax temperans skews neutrophil maturation and polarizes Th17 cells to promote lung adenocarcinoma development 嗜酸性粒细胞扭曲了中性粒细胞的成熟并使Th17细胞极化，从而促进了肺腺癌的发展

IF 6.2 2区医学

Oncogenesis Pub Date : 2024-04-03 DOI: 10.1038/s41389-024-00513-6

Joshua K. Stone, Natalia von Muhlinen, Chenran Zhang, Ana I. Robles, Amy L. Flis, Eleazar Vega-Valle, Akihiko Miyanaga, Masaru Matsumoto, K. Leigh Greathouse, Tomer Cooks, Giorgio Trinchieri, Curtis C. Harris

{"title":"Acidovorax temperans skews neutrophil maturation and polarizes Th17 cells to promote lung adenocarcinoma development","authors":"Joshua K. Stone, Natalia von Muhlinen, Chenran Zhang, Ana I. Robles, Amy L. Flis, Eleazar Vega-Valle, Akihiko Miyanaga, Masaru Matsumoto, K. Leigh Greathouse, Tomer Cooks, Giorgio Trinchieri, Curtis C. Harris","doi":"10.1038/s41389-024-00513-6","DOIUrl":"https://doi.org/10.1038/s41389-024-00513-6","url":null,"abstract":"Change within the intratumoral microbiome is a common feature in lung and other cancers and may influence inflammation and immunity in the tumor microenvironment, affecting growth and metastases. We previously characterized the lung cancer microbiome in patients and identified Acidovorax temperans as enriched in tumors. Here, we instilled A. temperans in an animal model driven by mutant K-ras and Tp53. This revealed A. temperans accelerates tumor development and burden through infiltration of proinflammatory cells. Neutrophils exposed to A. temperans displayed a mature, pro-tumorigenic phenotype with increased cytokine signaling, with a global shift away from IL-1β signaling. Neutrophil to monocyte and macrophage signaling upregulated MHC II to activate CD4+ T cells, polarizing them to an IL-17A+ phenotype detectable in CD4+ and γδ populations (T17). These T17 cells shared a common gene expression program predictive of poor survival in human LUAD. These data indicate bacterial exposure promotes tumor growth by modulating inflammation.<figure></figure>","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"53 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140600136","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

RIOK3 sustains colorectal cancer cell survival under glucose deprivation via an HSP90α-dependent pathway RIOK3 通过 HSP90α 依赖性途径维持葡萄糖剥夺条件下结直肠癌细胞的存活

IF 6.2 2区医学

Oncogenesis Pub Date : 2024-03-07 DOI: 10.1038/s41389-024-00514-5

Nan Zhang, Lu Dong, Tingting Ning, Feng Du, Mengran Zhao, Junxuan Xu, Sian Xie, Si Liu, Xiujing Sun, Peng Li, Shutian Zhang, Shengtao Zhu

{"title":"RIOK3 sustains colorectal cancer cell survival under glucose deprivation via an HSP90α-dependent pathway","authors":"Nan Zhang, Lu Dong, Tingting Ning, Feng Du, Mengran Zhao, Junxuan Xu, Sian Xie, Si Liu, Xiujing Sun, Peng Li, Shutian Zhang, Shengtao Zhu","doi":"10.1038/s41389-024-00514-5","DOIUrl":"https://doi.org/10.1038/s41389-024-00514-5","url":null,"abstract":"Glucose oxidation via the pentose phosphate pathway serves as the primary cellular mechanism for generating nicotinamide adenine dinucleotide phosphate (NADPH). The central regions of solid tumors typically experience glucose deficiency, emphasizing the need for sustained NADPH production crucial to tumor cell survival. This study highlights the crucial role of RIOK3 in maintaining NADPH production and colorectal cancer (CRC) cell survival during glucose deficiency. Our findings revealed upregulated RIOK3 expression upon glucose deprivation, with RIOK3 knockout significantly reducing cancer cell survival. Mechanistically, RIOK3 interacts with heat shock protein 90α (HSP90α), a chaperone integral to various cellular processes, thereby facilitating HSP90α binding to isocitrate dehydrogenase 1 (IDH1). This interaction further upregulates IDH1 expression, enhancing NADPH production and preserving redox balance. Furthermore, RIOK3 inhibition had no discernible effect on intracellular NADPH levels and cell death rates in HSP90α-knockdown cells. Collectively, our findings suggest that RIOK3 sustains colon cancer cell survival in low-glucose environments through an HSP90α-dependent pathway. This highlights the significance of the RIOK3–HSP90α–IDH1 cascade, providing insights into potential targeted therapeutic strategies for CRC in metabolic stress conditions.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"286 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140057699","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

Designing patient-oriented combination therapies for acute myeloid leukemia based on efficacy/toxicity integration and bipartite network modeling. 基于疗效/毒性整合和双向网络建模，设计以患者为导向的急性髓性白血病联合疗法。

IF 6.2 2区医学

Oncogenesis Pub Date : 2024-03-01 DOI: 10.1038/s41389-024-00510-9

Mehdi Mirzaie, Elham Gholizadeh, Juho J Miettinen, Filipp Ianevski, Tanja Ruokoranta, Jani Saarela, Mikko Manninen, Susanna Miettinen, Caroline A Heckman, Mohieddin Jafari

{"title":"Designing patient-oriented combination therapies for acute myeloid leukemia based on efficacy/toxicity integration and bipartite network modeling.","authors":"Mehdi Mirzaie, Elham Gholizadeh, Juho J Miettinen, Filipp Ianevski, Tanja Ruokoranta, Jani Saarela, Mikko Manninen, Susanna Miettinen, Caroline A Heckman, Mohieddin Jafari","doi":"10.1038/s41389-024-00510-9","DOIUrl":"10.1038/s41389-024-00510-9","url":null,"abstract":"Acute myeloid leukemia (AML), a heterogeneous and aggressive blood cancer, does not respond well to single-drug therapy. A combination of drugs is required to effectively treat this disease. Computational models are critical for combination therapy discovery due to the tens of thousands of two-drug combinations, even with approved drugs. While predicting synergistic drugs is the focus of current methods, few consider drug efficacy and potential toxicity, which are crucial for treatment success. To find effective new drug candidates, we constructed a bipartite network using patient-derived tumor samples and drugs. The network is based on drug-response screening and summarizes all treatment response heterogeneity as drug response weights. This bipartite network is then projected onto the drug part, resulting in the drug similarity network. Distinct drug clusters were identified using community detection methods, each targeting different biological processes and pathways as revealed by enrichment and pathway analysis of the drugs' protein targets. Four drugs with the highest efficacy and lowest toxicity from each cluster were selected and tested for drug sensitivity using cell viability assays on various samples. Results show that ruxolitinib-ulixertinib and sapanisertib-LY3009120 are the most effective combinations with the least toxicity and the best synergistic effect on blast cells. These findings lay the foundation for personalized and successful AML therapies, ultimately leading to the development of drug combinations that can be used alongside standard first-line AML treatment.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"13 1","pages":"11"},"PeriodicalIF":6.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10907624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013100","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

Progesterone receptor potentiates macropinocytosis through CDC42 in pancreatic ductal adenocarcinoma. 胰腺导管腺癌中的黄体酮受体通过 CDC42 强化大蛋白细胞增殖。

IF 6.2 2区医学

Oncogenesis Pub Date : 2024-02-29 DOI: 10.1038/s41389-024-00512-7

Ying-Na Liao, Yan-Zhi Gai, Li-Heng Qian, Hong Pan, Yi-Fan Zhang, Pin Li, Ying Guo, Shu-Xin Li, Hui-Zhen Nie

{"title":"Progesterone receptor potentiates macropinocytosis through CDC42 in pancreatic ductal adenocarcinoma.","authors":"Ying-Na Liao, Yan-Zhi Gai, Li-Heng Qian, Hong Pan, Yi-Fan Zhang, Pin Li, Ying Guo, Shu-Xin Li, Hui-Zhen Nie","doi":"10.1038/s41389-024-00512-7","DOIUrl":"10.1038/s41389-024-00512-7","url":null,"abstract":"Endocrine receptors play an essential role in tumor metabolic reprogramming and represent a promising therapeutic avenue in pancreatic ductal adenocarcinoma (PDAC). PDAC is characterized by a nutrient-deprived microenvironment. To meet their ascendant energy demands, cancer cells can internalize extracellular proteins via macropinocytosis. However, the roles of endocrine receptors in macropinocytosis are not clear. In this study, we found that progesterone receptor (PGR), a steroid-responsive nuclear receptor, is highly expressed in PDAC tissues obtained from both patients and transgenic LSL-KrasG12D/+; LSL-Trp53R172H/+; PDX1-cre (KPC) mice. Moreover, PGR knockdown restrained PDAC cell survival and tumor growth both in vitro and in vivo. Genetic and pharmacological PGR inhibition resulted in a marked attenuation of macropinocytosis in PDAC cells and subcutaneous tumor models, indicating the involvement of this receptor in macropinocytosis regulation. Mechanistically, PGR upregulated CDC42, a critical regulator in macropinocytosis, through PGR-mediated transcriptional activation. These data deepen the understanding of how the endocrine system influences tumor progression via a non-classical pathway and provide a novel therapeutic option for patients with PDAC.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"13 1","pages":"10"},"PeriodicalIF":6.2,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10904380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139997026","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

PKC-independent PI3K signalling diminishes PKC inhibitor sensitivity in uveal melanoma 不依赖 PKC 的 PI3K 信号降低了葡萄膜黑色素瘤对 PKC 抑制剂的敏感性

IF 6.2 2区医学

Oncogenesis Pub Date : 2024-02-28 DOI: 10.1038/s41389-024-00511-8

John J. Park, Sabine Abou Hamad, Ashleigh Stewart, Matteo S. Carlino, Su Yin Lim, Helen Rizos

{"title":"PKC-independent PI3K signalling diminishes PKC inhibitor sensitivity in uveal melanoma","authors":"John J. Park, Sabine Abou Hamad, Ashleigh Stewart, Matteo S. Carlino, Su Yin Lim, Helen Rizos","doi":"10.1038/s41389-024-00511-8","DOIUrl":"https://doi.org/10.1038/s41389-024-00511-8","url":null,"abstract":"Protein kinase C (PKC) is activated downstream of gain-of-function GNAQ or GNA11 (GNAQ/GNA11) mutations in over 90% of uveal melanoma (UM). Phase I clinical trials of PKC inhibitors have shown modest response rates with no survival benefit in metastatic UM. Although PKC inhibitors actively suppress mitogen-activated protein kinase (MAPK) signalling in UM, the effect on other UM signalling cascades is not well understood. We examined the transcriptome of UM biopsies collected pre- and post-PKC inhibitor therapy and confirmed that MAPK, but not PI3K/AKT signalling, was inhibited early during treatment with the second-generation PKC inhibitor IDE196. Similarly, in GNAQ/GNA11-mutant UM cell models, PKC inhibitor monotherapy effectively suppressed MAPK activity, but PI3K/AKT signalling remained active, and thus, concurrent inhibition of PKC and PI3K/AKT signalling was required to synergistically induce cell death in a panel of GNAQ/GNA11-mutant UM cell lines. We also show that re-activation of MAPK signalling has a dominant role in regulating PKC inhibitor responses in UM and that PI3K/AKT signalling diminishes UM cell sensitivity to PKC inhibitor monotherapy. Thus, combination therapies targeting PKC and PKC-independent signalling nodes, including PI3K/AKT activity, are required to improve responses in patients with metastatic UM.<figure></figure>","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"82 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139987822","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

DDX3X interacts with SIRT7 to promote PD-L1 expression to facilitate PDAC progression DDX3X 与 SIRT7 相互作用，促进 PD-L1 的表达，从而推动 PDAC 的进展

IF 6.2 2区医学

Oncogenesis Pub Date : 2024-02-05 DOI: 10.1038/s41389-024-00509-2

Tianming Zhao, Hanlong Zhu, Tianhui Zou, Si Zhao, Lin Zhou, Muhan Ni, Feng Liu, Hao Zhu, Xiaotan Dou, Jian Di, Bing Xu, Lei Wang, Xiaoping Zou

{"title":"DDX3X interacts with SIRT7 to promote PD-L1 expression to facilitate PDAC progression","authors":"Tianming Zhao, Hanlong Zhu, Tianhui Zou, Si Zhao, Lin Zhou, Muhan Ni, Feng Liu, Hao Zhu, Xiaotan Dou, Jian Di, Bing Xu, Lei Wang, Xiaoping Zou","doi":"10.1038/s41389-024-00509-2","DOIUrl":"https://doi.org/10.1038/s41389-024-00509-2","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3>Pancreatic ductal adenocarcinoma (PDAC) is recognized as the most aggressive and fatal malignancy. A previous study reported that PDAC patients who exhibit elevated levels of DDX3X have a poor prognosis and low overall survival rate. However, the underlying molecular mechanism remains unclear. This study aimed to investigate the specific roles of DDX3X in PDAC. Multiple bioinformatics analyses were used to evaluate DDX3X expression and its potential role in PDAC. In vitro and in vivo studies were performed to assess the effects of DDX3X on PDAC cell growth. Furthermore, Western blotting, quantitative PCR, immunohistochemistry, immunofluorescence, mass spectrometry, coimmunoprecipitation and multiplexed immunohistochemical staining were conducted to identify the specific regulatory mechanism in PDAC. The results verified that DDX3X expression is notably upregulated in the tumor tissue vs. normal tissue of PDAC patients. DDX3X knockdown markedly suppressed the proliferation, invasion and migration of PDAC cells in vitro and inhibited tumor growth in vivo. Conversely, overexpression of DDX3X induced the opposite effect. Further studies supported that the DDX3X protein can associate with sirtuin 7 (SIRT7) to stimulate PDAC carcinogenesis and progression. Furthermore, SIRT7 inhibition significantly impeded DDX3X-mediated tumor growth both ex vivo and in vivo. The results also revealed that programmed death ligand 1 (PD-L1) expression is positively correlated with DDX3X expression. These results reveal significant involvement of the DDX3X-SIRT7 axis in the initiation and advancement of PDAC and offer previously undiscovered therapeutic options for PDAC management.<figure></figure>","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"731 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139688969","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

LUBAC promotes angiogenesis and lung tumorigenesis by ubiquitinating and antagonizing autophagic degradation of HIF1α LUBAC 通过泛素化和拮抗 HIF1α 的自噬降解促进血管生成和肺肿瘤发生

IF 6.2 2区医学

Oncogenesis Pub Date : 2024-01-25 DOI: 10.1038/s41389-024-00508-3

Ying Jin, Yazhi Peng, Jie Xu, Ye Yuan, Nan Yang, Zemei Zhang, Lei Xu, Lin Li, Yulian Xiong, Dejiao Sun, Yamu Pan, Ruiqing Wu, Jian Fu

{"title":"LUBAC promotes angiogenesis and lung tumorigenesis by ubiquitinating and antagonizing autophagic degradation of HIF1α","authors":"Ying Jin, Yazhi Peng, Jie Xu, Ye Yuan, Nan Yang, Zemei Zhang, Lei Xu, Lin Li, Yulian Xiong, Dejiao Sun, Yamu Pan, Ruiqing Wu, Jian Fu","doi":"10.1038/s41389-024-00508-3","DOIUrl":"https://doi.org/10.1038/s41389-024-00508-3","url":null,"abstract":"Hypoxia-inducible factor 1 (HIF1) is critically important for driving angiogenesis and tumorigenesis. Linear ubiquitin chain assembly complex (LUBAC), the only known ubiquitin ligase capable of catalyzing protein linear ubiquitination to date, is implicated in cell signaling and associated with cancers. However, the role and mechanism of LUBAC in regulating the expression and function of HIF1α, the labile subunit of HIF1, remain to be elucidated. Herein we showed that LUBAC increases HIF1α protein expression in cultured cells and tissues of human lung cancer and enhances HIF1α DNA-binding and transcriptional activities, which are dependent upon LUBAC enzymatic activity. Mechanistically, LUBAC increases HIF1α stability through antagonizing HIF1α decay by the chaperone-mediated autophagy (CMA)-lysosome pathway, thereby potentiating HIF1α activity. We further demonstrated that HIF1α selectively interacts with HOIP (the catalytic subunit of LUBAC) primarily in the cytoplasm. LUBAC catalyzes linear ubiquitination of HIF1α at lysine 362. Linear ubiquitination shields HIF1α from interacting with heat-shock cognate protein of 70 kDa and lysosome-associated membrane protein type 2 A, two components of CMA. Consequently, linear ubiquitination confers protection against CMA-mediated destruction of HIF1α, increasing HIF1α stability and activity. We found that prolyl hydroxylation is not a perquisite for LUBAC’s effects on HIF1α. Functionally, LUBAC facilitates proliferation, clonogenic formation, invasion and migration of lung cancer cells. LUBAC also boosts angiogenesis and exacerbates lung cancer growth in mice, which are greatly compromised by inhibition of HIF1α. This work provides novel mechanistic insights into the role of LUBAC in regulating HIF1α homeostasis, tumor angiogenesis and tumorigenesis of lung cancer, making LUBAC an attractive therapeutic target for cancers.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"34 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139552430","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

Preneoplastic cells switch to Warburg metabolism from their inception exposing multiple vulnerabilities for targeted elimination. 癌前病变细胞从一开始就转入沃伯格新陈代谢，暴露出多种弱点，需要有针对性地加以消除。

IF 5.9 2区医学

Oncogenesis Pub Date : 2024-01-25 DOI: 10.1038/s41389-024-00507-4

Henna Myllymäki, Lisa Kelly, Abigail M Elliot, Roderick N Carter, Jeanette Astorga Johansson, Kai Yee Chang, Justyna Cholewa-Waclaw, Nicholas M Morton, Yi Feng

{"title":"Preneoplastic cells switch to Warburg metabolism from their inception exposing multiple vulnerabilities for targeted elimination.","authors":"Henna Myllymäki, Lisa Kelly, Abigail M Elliot, Roderick N Carter, Jeanette Astorga Johansson, Kai Yee Chang, Justyna Cholewa-Waclaw, Nicholas M Morton, Yi Feng","doi":"10.1038/s41389-024-00507-4","DOIUrl":"10.1038/s41389-024-00507-4","url":null,"abstract":"Otto Warburg described tumour cells as displaying enhanced aerobic glycolysis whilst maintaining defective oxidative phosphorylation (OXPHOS) for energy production almost 100 years ago [1, 2]. Since then, the 'Warburg effect' has been widely accepted as a key feature of rapidly proliferating cancer cells [3-5]. What is not clear is how early \"Warburg metabolism\" initiates in cancer and whether changes in energy metabolism might influence tumour progression ab initio. We set out to investigate energy metabolism in the HRASG12V driven preneoplastic cell (PNC) at inception, in a zebrafish skin PNC model. We find that, within 24 h of HRASG12V induction, PNCs upregulate glycolysis and blocking glycolysis reduces PNC proliferation, whilst increasing available glucose enhances PNC proliferation and reduces apoptosis. Impaired OXPHOS accompanies enhanced glycolysis in PNCs, and a mild complex I inhibitor, metformin, selectively suppresses expansion of PNCs. Enhanced mitochondrial fragmentation might be underlining impaired OXPHOS and blocking mitochondrial fragmentation triggers PNC apoptosis. Our data indicate that altered energy metabolism is one of the earliest events upon oncogene activation in somatic cells, which allows a targeted and effective PNC elimination.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"13 1","pages":"7"},"PeriodicalIF":5.9,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10810875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139564494","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

Correction: TRIM11 facilitates chemoresistance in nasopharyngeal carcinoma by activating the β-catenin/ABCC9 axis via p62-selective autophagic degradation of Daple. 更正：TRIM11通过p62选择性自噬降解Daple，激活β-catenin/ABCC9轴，从而促进鼻咽癌的化疗耐药性。

IF 6.2 2区医学

Oncogenesis Pub Date : 2024-01-10 DOI: 10.1038/s41389-023-00506-x

Runa Zhang, Si-Wei Li, Lijuan Liu, Jun Yang, Guofu Huang, Yi Sang

引用次数: 0

SMYD3 promotes endometrial cancer through epigenetic regulation of LIG4/XRCC4/XLF complex in non-homologous end joining repair SMYD3 在非同源末端连接修复中通过对 LIG4/XRCC4/XLF 复合物的表观遗传调控促进子宫内膜癌的发生

IF 6.2 2区医学

Oncogenesis Pub Date : 2024-01-08 DOI: 10.1038/s41389-023-00503-0

Yujia Huang, Ming Tang, Zhiyi Hu, Bailian Cai, Guofang Chen, Lijun Jiang, Yan Xia, Pujun Guan, Xiaoqi Li, Zhiyong Mao, Xiaoping Wan, Wen Lu

{"title":"SMYD3 promotes endometrial cancer through epigenetic regulation of LIG4/XRCC4/XLF complex in non-homologous end joining repair","authors":"Yujia Huang, Ming Tang, Zhiyi Hu, Bailian Cai, Guofang Chen, Lijun Jiang, Yan Xia, Pujun Guan, Xiaoqi Li, Zhiyong Mao, Xiaoping Wan, Wen Lu","doi":"10.1038/s41389-023-00503-0","DOIUrl":"https://doi.org/10.1038/s41389-023-00503-0","url":null,"abstract":"Endometrial cancer (EC) stands as one of the most prevalent malignancies affecting the female genital tract, witnessing a rapid surge in incidence globally. Despite the well-established association of histone methyltransferase SMYD3 with the development and progression of various cancers, its specific oncogenic role in endometrial cancer remains unexplored. In the present study, we report that the expression level of SMYD3 is significantly upregulated in EC samples and associated with EC progression. Through meticulous in vivo and in vitro experiments, we reveal that depletion of SMYD3 curtails cell proliferation, migration, and invasion capabilities, leading to compromised non-homologous end joining repair (NHEJ) and heightened sensitivity of EC cells to radiation. Furthermore, our pathway enrichment analysis underscores the pivotal involvement of the DNA damage repair pathway in regulating EC progression. Mechanistically, in response to DNA damage, SMYD3 is recruited to these sites in a PARP1-dependent manner, specifically methylating LIG4. This methylation sets off a sequential assembly of the LIG4/XRCC4/XLF complex, actively participating in the NHEJ pathway and thereby fostering EC progression. Notably, our findings highlight the promise of SMYD3 as a crucial player in NHEJ repair and its direct correlation with EC progression. Intriguingly, pharmacological intervention targeting SMYD3 with its specific inhibitor, BCI-121, emerges as a potent strategy, markedly suppressing the tumorigenicity of EC cells and significantly enhancing the efficacy of radiotherapy. Collectively, our comprehensive data position SMYD3 as a central factor in NHEJ repair and underscore its potential as a promising pharmacological target for endometrial cancer therapy, validated through both in vitro and in vivo systems.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"34 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139397205","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