Oncogenesis最新文献_第10页

Chemotherapy-induced executioner caspase activation increases breast cancer malignancy through epigenetic de-repression of CDH12. 化疗诱导的刽子手caspase激活通过表观遗传去抑制CDH12增加乳腺癌恶性肿瘤。

IF 6.2 2区医学

Oncogenesis Pub Date : 2023-06-24 DOI: 10.1038/s41389-023-00479-x

Yuxing Wang, Ru Wang, Xiaohe Liu, Menghao Liu, Lili Sun, Xiaohua Pan, Huili Hu, Baichun Jiang, Yongxin Zou, Qiao Liu, Yaoqin Gong, Molin Wang, Gongping Sun

{"title":"Chemotherapy-induced executioner caspase activation increases breast cancer malignancy through epigenetic de-repression of CDH12.","authors":"Yuxing Wang, Ru Wang, Xiaohe Liu, Menghao Liu, Lili Sun, Xiaohua Pan, Huili Hu, Baichun Jiang, Yongxin Zou, Qiao Liu, Yaoqin Gong, Molin Wang, Gongping Sun","doi":"10.1038/s41389-023-00479-x","DOIUrl":"https://doi.org/10.1038/s41389-023-00479-x","url":null,"abstract":"Cancer relapse and metastasis are major obstacles for effective treatment. One important mechanism to eliminate cancer cells is to induce apoptosis. Activation of executioner caspases is the key step in apoptosis and was considered \"a point of no return\". However, in recent years, accumulating evidence has demonstrated that cells can survive executioner caspase activation in response to apoptotic stimuli through a process named anastasis. Here we show that breast cancer cells that have survived through anastasis (anastatic cells) after exposure to chemotherapeutic drugs acquire enhanced proliferation and migration. Mechanistically, cadherin 12 (CDH12) is persistently upregulated in anastatic cells and promotes breast cancer malignancy via activation of ERK and CREB. Moreover, we demonstrate that executioner caspase activation induced by chemotherapeutic drugs results in loss of DNA methylation and repressive histone modifications in the CDH12 promoter region, leading to increased CDH12 expression. Our work unveils the mechanism underlying anastasis-induced enhancement in breast cancer malignancy, offering new therapeutic targets for preventing post-chemotherapy cancer relapse and metastasis.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"34"},"PeriodicalIF":6.2,"publicationDate":"2023-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10290709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10090749","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: 2

Antibody-based binding domain fused to TCRγ chain facilitates T cell cytotoxicity for potent anti-tumor response. 基于抗体的结合域与TCRγ链融合，促进T细胞的细胞毒性，从而产生有效的抗肿瘤反应。

IF 6.2 2区医学

Oncogenesis Pub Date : 2023-06-22 DOI: 10.1038/s41389-023-00480-4

Zhao Chen, Changyou Lin, Hong Pei, Xiaomei Yuan, Jia Xu, Mingwei Zou, Xinyuan Zhang, Amber Fossier, Meizhu Liu, Seungah Goo, Lei Lei, Jia Yang, Catherine Novick, Jiqing Xu, Ge Ying, Zhihong Zhou, Jianbo Wu, Chunyi Tang, Wenying Zhang, Zhenping Wang, Zhihao Wang, Huitang Zhang, Wenzhong Guo, Qidong Hu, Henry Ji, Runqiang Chen

{"title":"Antibody-based binding domain fused to TCRγ chain facilitates T cell cytotoxicity for potent anti-tumor response.","authors":"Zhao Chen, Changyou Lin, Hong Pei, Xiaomei Yuan, Jia Xu, Mingwei Zou, Xinyuan Zhang, Amber Fossier, Meizhu Liu, Seungah Goo, Lei Lei, Jia Yang, Catherine Novick, Jiqing Xu, Ge Ying, Zhihong Zhou, Jianbo Wu, Chunyi Tang, Wenying Zhang, Zhenping Wang, Zhihao Wang, Huitang Zhang, Wenzhong Guo, Qidong Hu, Henry Ji, Runqiang Chen","doi":"10.1038/s41389-023-00480-4","DOIUrl":"https://doi.org/10.1038/s41389-023-00480-4","url":null,"abstract":"Chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated potent clinical efficacy in the treatment of hematopoietic malignancies. However, the application of CAR-T in solid tumors has been limited due in part to the expression of inhibitory molecules in the tumor microenvironment, leading to T-cell exhaustion. To overcome this limitation, we have developed a synthetic T-cell receptor (TCR) that targets programmed death-ligand 1 (PD-L1), a molecule that is widely expressed in various solid tumors and plays a pivotal role in T-cell exhaustion. Our novel TCR platform is based on antibody-based binding domain, which is typically a single-chain variable fragment (scFv), fused to the γδ TCRs (TCRγδ). We have utilized the T-cell receptor alpha constant (TRAC) locus editing approach to express cell surface scFv of anti-PD-L1, which is fused to the constant region of the TCRγ or TCRδ chain in activated T cells derived from peripheral blood mononuclear cells (PBMCs). Our results indicate that these reconfigured receptors, both γ-TCRγδ and δ-TCRγδ, have the capability to transduce signals, produce inflammatory cytokines, degranulate and exert tumor killing activity upon engagement with PD-L1 antigen in vitro. Additionally, we have also shown that γ-TCRγδ exerted superior efficacy than δ-TCRγδ in in vivo xenograft model.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"33"},"PeriodicalIF":6.2,"publicationDate":"2023-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10287668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9709831","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

WDR5 facilitates recruitment of N-MYC to conserved WDR5 gene targets in neuroblastoma cell lines. WDR5促进神经母细胞瘤细胞系中N-MYC向保守的WDR5基因靶标的募集。

IF 6.2 2区医学

Oncogenesis Pub Date : 2023-06-19 DOI: 10.1038/s41389-023-00477-z

Leigh A Bumpous, Kylie C Moe, Jing Wang, Logan A Carver, Alexandria G Williams, Alexander S Romer, Jesse D Scobee, Jack N Maxwell, Cheyenne A Jones, Dai H Chung, William P Tansey, Qi Liu, April M Weissmiller

{"title":"WDR5 facilitates recruitment of N-MYC to conserved WDR5 gene targets in neuroblastoma cell lines.","authors":"Leigh A Bumpous, Kylie C Moe, Jing Wang, Logan A Carver, Alexandria G Williams, Alexander S Romer, Jesse D Scobee, Jack N Maxwell, Cheyenne A Jones, Dai H Chung, William P Tansey, Qi Liu, April M Weissmiller","doi":"10.1038/s41389-023-00477-z","DOIUrl":"10.1038/s41389-023-00477-z","url":null,"abstract":"Collectively, the MYC family of oncoprotein transcription factors is overexpressed in more than half of all malignancies. The ability of MYC proteins to access chromatin is fundamental to their role in promoting oncogenic gene expression programs in cancer and this function depends on MYC-cofactor interactions. One such cofactor is the chromatin regulator WDR5, which in models of Burkitt lymphoma facilitates recruitment of the c-MYC protein to chromatin at genes associated with protein synthesis, allowing for tumor progression and maintenance. However, beyond Burkitt lymphoma, it is unknown whether these observations extend to other cancers or MYC family members, and whether WDR5 can be deemed as a \"universal\" MYC recruiter. Here, we focus on N-MYC amplified neuroblastoma to determine the extent of colocalization between N-MYC and WDR5 on chromatin while also demonstrating that like c-MYC, WDR5 can facilitate the recruitment of N-MYC to conserved WDR5-bound genes. We conclude based on this analysis that N-MYC and WDR5 colocalize invariantly across cell lines at predicted sites of facilitated recruitment associated with protein synthesis genes. Surprisingly, we also identify N-MYC-WDR5 cobound genes that are associated with DNA repair and cell cycle processes. Dissection of chromatin binding characteristics for N-MYC and WDR5 at all cobound genes reveals that sites of facilitated recruitment are inherently different than most N-MYC-WDR5 cobound sites. Our data reveals that WDR5 acts as a universal MYC recruiter at a small cohort of previously identified genes and highlights novel biological functions that may be coregulated by N-MYC and WDR5 to sustain the neuroblastoma state.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"32"},"PeriodicalIF":6.2,"publicationDate":"2023-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10279693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10084959","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

Integrated analysis of single-cell and bulk RNA sequencing data reveals an immunostimulatory microenvironment in tumor thrombus of osteosarcoma. 单细胞和大量RNA测序数据的综合分析揭示了骨肉瘤肿瘤血栓中的免疫刺激微环境。

IF 6.2 2区医学

Oncogenesis Pub Date : 2023-05-27 DOI: 10.1038/s41389-023-00474-2

Tao Ji, Qianyu Shi, Song Mei, Jiuhui Xu, Haijie Liang, Lu Xie, Tingting Ren, Kunkun Sun, Dasen Li, Xiaodong Tang, Peng Zhang, Wei Guo

{"title":"Integrated analysis of single-cell and bulk RNA sequencing data reveals an immunostimulatory microenvironment in tumor thrombus of osteosarcoma.","authors":"Tao Ji, Qianyu Shi, Song Mei, Jiuhui Xu, Haijie Liang, Lu Xie, Tingting Ren, Kunkun Sun, Dasen Li, Xiaodong Tang, Peng Zhang, Wei Guo","doi":"10.1038/s41389-023-00474-2","DOIUrl":"https://doi.org/10.1038/s41389-023-00474-2","url":null,"abstract":"Tumor thrombus of bone sarcomas represents a unique reservoir for various types of cancer and immune cells, however, the investigation of tumor thrombus at a single-cell level is very limited. And it is still an open question to identify the thrombus-specific tumor microenvironment that is associated with the tumor-adaptive immune response. Here, by analyzing bulk tissue and single-cell level transcriptome from the paired thrombus and primary tumor samples of osteosarcoma (OS) patients, we define the immunostimulatory microenvironment in tumor thrombus of OS with a higher proportion of tumor-associated macrophages with M1-like states (TAM-M1) and TAM-M1 with high expression of CCL4. OS tumor thrombus is found to have upregulated IFN-γ and TGF-β signalings that are related to immune surveillance of circulating tumor cells in blood circulation. Further multiplexed immunofluorescence staining of the CD3/CD4/CD8A/CD68/CCL4 markers validates the immune-activated state in the tumor thrombus samples. Our study first reports the transcriptome differences at a single-cell level between tumor thrombus and primary tumor in sarcoma.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"31"},"PeriodicalIF":6.2,"publicationDate":"2023-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10224931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9533216","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: 2

CDK4/6 inhibitors and the pRB-E2F1 axis suppress PVR and PD-L1 expression in triple-negative breast cancer. CDK4/6抑制剂和pRB-E2F1轴抑制三阴性乳腺癌中PVR和PD-L1的表达。

IF 6.2 2区医学

Oncogenesis Pub Date : 2023-05-26 DOI: 10.1038/s41389-023-00475-1

Mariusz Shrestha, Dong-Yu Wang, Yaacov Ben-David, Eldad Zacksenhaus

{"title":"CDK4/6 inhibitors and the pRB-E2F1 axis suppress PVR and PD-L1 expression in triple-negative breast cancer.","authors":"Mariusz Shrestha, Dong-Yu Wang, Yaacov Ben-David, Eldad Zacksenhaus","doi":"10.1038/s41389-023-00475-1","DOIUrl":"https://doi.org/10.1038/s41389-023-00475-1","url":null,"abstract":"Immune-checkpoint (IC) modulators like the poliovirus receptor (PVR) and programmed death ligand 1 (PD-L1) attenuate innate and adaptive immune responses and are potential therapeutic targets for diverse malignancies, including triple-negative breast cancer (TNBC). The retinoblastoma tumor suppressor, pRB, controls cell growth through E2F1-3 transcription factors, and its inactivation drives metastatic cancer, yet its effect on IC modulators is contentious. Here, we show that RB-loss and high E2F1/E2F2 signatures correlate with expression of PVR, CD274 (PD-L1 gene) and other IC modulators and that pRB represses whereas RB depletion and E2F1 induce PVR and CD274 in TNBC cells. Accordingly, the CDK4/6 inhibitor, palbociclib, suppresses both PVR and PD-L1 expression. Palbociclib also counteracts the effect of CDK4 on SPOP, leading to its depletion, but the overall effect of palbociclib is a net reduction in PD-L1 level. Hydrochloric acid, commonly used to solubilize palbociclib, counteracts its effect and induces PD-L1 expression. Remarkably, lactic acid, a by-product of glycolysis, also induces PD-L1 as well as PVR. Our results suggest a model in which CDK4/6 regulates PD-L1 turnover by promoting its transcription via pRB-E2F1 and degradation via SPOP and that the CDK4/6-pRB-E2F pathway couples cell proliferation with the induction of multiple innate and adaptive immunomodulators, with direct implications for cancer progression, anti-CDK4/6- and IC-therapies.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"29"},"PeriodicalIF":6.2,"publicationDate":"2023-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10213015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9531118","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: 4

Phosphorylation of IWS1 by AKT maintains liposarcoma tumor heterogeneity through preservation of cancer stem cell phenotypes and mesenchymal-epithelial plasticity. AKT磷酸化IWS1通过维持肿瘤干细胞表型和间充质上皮可塑性来维持脂肪肉瘤肿瘤的异质性。

IF 6.2 2区医学

Oncogenesis Pub Date : 2023-05-26 DOI: 10.1038/s41389-023-00469-z

Yu Wang, Hongji Zhang, Alessandro La Ferlita, Nipin Sp, Marina Goryunova, Patricia Sarchet, Zhiwei Hu, Michael Sorkin, Alex Kim, Hai Huang, Hua Zhu, Allan Tsung, Raphael E Pollock, Joal D Beane

{"title":"Phosphorylation of IWS1 by AKT maintains liposarcoma tumor heterogeneity through preservation of cancer stem cell phenotypes and mesenchymal-epithelial plasticity.","authors":"Yu Wang, Hongji Zhang, Alessandro La Ferlita, Nipin Sp, Marina Goryunova, Patricia Sarchet, Zhiwei Hu, Michael Sorkin, Alex Kim, Hai Huang, Hua Zhu, Allan Tsung, Raphael E Pollock, Joal D Beane","doi":"10.1038/s41389-023-00469-z","DOIUrl":"https://doi.org/10.1038/s41389-023-00469-z","url":null,"abstract":"Chemotherapy remains the mainstay of treatment for patients with advanced liposarcoma (LPS), but response rates are only 25% and the overall survival at 5 years is dismal at 20-34%. Translation of other therapies have not been successful and there has been no significant improvement in prognosis for nearly 20 years. The aberrant activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been implicated in the aggressive clinical behavior LPS and in resistance to chemotherapy, but the precise mechanism remains elusive and efforts to target AKT clinically have failed. Here we show that the AKT-mediated phosphorylation of the transcription elongation factor IWS1, promotes the maintenance of cancer stem cells in both cell and xenograft models of LPS. In addition, phosphorylation of IWS1 by AKT contributes to a \"metastable\" cell phenotype, characterized by mesenchymal/epithelial plasticity. The expression of phosphorylated IWS1 also promotes anchorage-dependent and independent growth, cell migration, invasion, and tumor metastasis. In patients with LPS, IWS1 expression is associated with reduced overall survival, increased frequency of recurrence, and shorter time to relapse after resection. These findings indicate that IWS1-mediated transcription elongation is an important regulator of human LPS pathobiology in an AKT-dependent manner and implicate IWS1 as an important molecular target to treat LPS.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"30"},"PeriodicalIF":6.2,"publicationDate":"2023-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10219984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9902904","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: 1

Circlehunter: a tool to identify extrachromosomal circular DNA from ATAC-Seq data. Circlehunter:从ATAC-Seq数据中识别染色体外环状DNA的工具。

IF 6.2 2区医学

Oncogenesis Pub Date : 2023-05-22 DOI: 10.1038/s41389-023-00476-0

Manqiu Yang, Shufan Zhang, Rong Jiang, Shaomu Chen, Moli Huang

{"title":"Circlehunter: a tool to identify extrachromosomal circular DNA from ATAC-Seq data.","authors":"Manqiu Yang, Shufan Zhang, Rong Jiang, Shaomu Chen, Moli Huang","doi":"10.1038/s41389-023-00476-0","DOIUrl":"https://doi.org/10.1038/s41389-023-00476-0","url":null,"abstract":"In cancer, extrachromosomal circular DNA (ecDNA), or megabase-pair amplified circular DNA, plays an essential role in intercellular heterogeneity and tumor cell revolution because of its non-Mendelian inheritance. We developed circlehunter ( https://github.com/suda-huanglab/circlehunter ), a tool for identifying ecDNA from ATAC-Seq data using the enhanced chromatin accessibility of ecDNA. Using simulated data, we showed that circlehunter has an F1 score of 0.93 at 30× local depth and read lengths as short as 35 bp. Based on 1312 ecDNAs predicted from 94 publicly available datasets of ATAC-Seq assays, we found 37 oncogenes contained in these ecDNAs with amplification characteristics. In small cell lung cancer cell lines, ecDNA containing MYC leads to amplification of MYC and cis-regulates the expression of NEUROD1, resulting in an expression pattern consistent with the NEUROD1 high expression subtype and sensitive to Aurora kinase inhibitors. This showcases that circlehunter could serve as a valuable pipeline for the investigation of tumorigenesis.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"28"},"PeriodicalIF":6.2,"publicationDate":"2023-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10202962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9516110","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: 2

Correction: USP53 plays an antitumor role in hepatocellular carcinoma through deubiquitination of cytochrome c. 更正:USP53通过去泛素化细胞色素c在肝癌中发挥抗肿瘤作用。

IF 6.2 2区医学

Oncogenesis Pub Date : 2023-05-15 DOI: 10.1038/s41389-023-00470-6

Ye Yao, Weijie Ma, Yonghua Guo, Yingyi Liu, Peng Xia, Xiaoling Wu, Yiran Chen, Kunlei Wang, Chengjie Mei, Ganggang Wang, Xiaomian Li, Zhonglin Zhang, Xi Chen, Yufeng Yuan

引用次数: 0

Dual role of ANGPTL8 in promoting tumor cell proliferation and immune escape during hepatocarcinogenesis. 肝癌发生过程中ANGPTL8在促进肿瘤细胞增殖和免疫逃逸中的双重作用。

IF 6.2 2区医学

Oncogenesis Pub Date : 2023-05-15 DOI: 10.1038/s41389-023-00473-3

Yujiu Gao, Yue Yuan, Shu Wen, Yanghui Chen, Zongli Zhang, Ying Feng, Bin Jiang, Shinan Ma, Rong Hu, Chen Fang, Xuzhi Ruan, Yahong Yuan, Xinggang Fang, Chao Luo, Zhongji Meng, Xiaoli Wang, Xingrong Guo

{"title":"Dual role of ANGPTL8 in promoting tumor cell proliferation and immune escape during hepatocarcinogenesis.","authors":"Yujiu Gao, Yue Yuan, Shu Wen, Yanghui Chen, Zongli Zhang, Ying Feng, Bin Jiang, Shinan Ma, Rong Hu, Chen Fang, Xuzhi Ruan, Yahong Yuan, Xinggang Fang, Chao Luo, Zhongji Meng, Xiaoli Wang, Xingrong Guo","doi":"10.1038/s41389-023-00473-3","DOIUrl":"https://doi.org/10.1038/s41389-023-00473-3","url":null,"abstract":"The interplay between hepatocellular carcinoma (HCC) cells and the tumor microenvironment is essential for hepatocarcinogenesis, but their contributions to HCC development are incompletely understood. We assessed the role of ANGPTL8, a protein secreted by HCC cells, in hepatocarcinogenesis and the mechanisms through which ANGPTL8 mediates crosstalk between HCC cells and tumor-associated macrophages. Immunohistochemical, Western blotting, RNA-Seq, and flow cytometry analyses of ANGPTL8 were performed. A series of in vitro and in vivo experiments were conducted to reveal the role of ANGPTL8 in the progression of HCC. ANGPTL8 expression was positively correlated with tumor malignancy in HCC, and high ANGPTL8 expression was associated with poor overall survival (OS) and disease-free survival (DFS). ANGPTL8 promoted HCC cell proliferation in vitro and in vivo, and ANGPTL8 KO inhibited the development of HCC in both DEN-induced and DEN-plus-CCL4-induced mouse HCC tumors. Mechanistically, the ANGPTL8-LILRB2/PIRB interaction promoted polarization of macrophages to the immunosuppressive M2 phenotype in macrophages and recruited immunosuppressive T cells. In hepatocytes, ANGPTL8-mediated stimulation of LILRB2/PIRB regulated the ROS/ERK pathway and upregulated autophagy, leading to the proliferation of HCC cells. Our data support the notion that ANGPTL8 has a dual role in promoting tumor cell proliferation and immune escape during hepatocarcinogenesis.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"26"},"PeriodicalIF":6.2,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10185523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9539530","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: 1

miR-137-LAPTM4B regulates cytoskeleton organization and cancer metastasis via the RhoA-LIMK-Cofilin pathway in osteosarcoma. miR-137-LAPTM4B在骨肉瘤中通过RhoA-LIMK-Cofilin通路调控细胞骨架组织和肿瘤转移。

IF 6.2 2区医学

Oncogenesis Pub Date : 2023-05-06 DOI: 10.1038/s41389-023-00471-5

Ruyu Yan, Dan Liu, Junjie Wang, Minxia Liu, Hongjuan Guo, Jing Bai, Shuo Yang, Jun Chang, Zhihong Yao, Zuozhang Yang, Tomas Blom, Kecheng Zhou

{"title":"miR-137-LAPTM4B regulates cytoskeleton organization and cancer metastasis via the RhoA-LIMK-Cofilin pathway in osteosarcoma.","authors":"Ruyu Yan, Dan Liu, Junjie Wang, Minxia Liu, Hongjuan Guo, Jing Bai, Shuo Yang, Jun Chang, Zhihong Yao, Zuozhang Yang, Tomas Blom, Kecheng Zhou","doi":"10.1038/s41389-023-00471-5","DOIUrl":"https://doi.org/10.1038/s41389-023-00471-5","url":null,"abstract":"Osteosarcoma (OS) is a rare malignant bone tumor but is one leading cause of cancer mortality in childhood and adolescence. Cancer metastasis accounts for the primary reason for treatment failure in OS patients. The dynamic organization of the cytoskeleton is fundamental for cell motility, migration, and cancer metastasis. Lysosome Associated Protein Transmembrane 4B (LAPTM4B) is an oncogene participating in various biological progress central to cancer biogenesis. However, the potential roles of LAPTM4B in OS and the related mechanisms remain unknown. Here, we established the elevated LAPTM4B expression in OS, and it is essential in regulating stress fiber organization through RhoA-LIMK-cofilin signaling pathway. In terms of mechanism, our data revealed that LAPTM4B promotes RhoA protein stability by suppressing the ubiquitin-mediated proteasome degradation pathway. Moreover, our data show that miR-137, rather than gene copy number and methylation status, contributes to the upregulation of LAPTM4B in OS. We report that miR-137 is capable of regulating stress fiber arrangement, OS cell migration, and metastasis via targeting LAPTM4B. Combining results from cells, patients' tissue samples, the animal model, and cancer databases, this study further suggests that the miR-137-LAPTM4B axis represents a clinically relevant pathway in OS progression and a viable target for novel therapeutics.","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"12 1","pages":"25"},"PeriodicalIF":6.2,"publicationDate":"2023-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10163001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9797994","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: 2