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| 1 | An isoflavone derivative potently inhibits the angiogenesis and progression of triple-negative breast cancer by targeting the MTA2/SerRS/VEGFA pathway显示文摘Objective:Angiogenesis plays a vital role in tumor growth and metastasis.Here,we aimed to find novel efficient antiangiogenic molecules targeting vascular endothelial growth factor A(VEGFA)at the transcriptional level to treat triple-negative breast cancer(TNBC).Methods:We used a cell-based seryl tRNA synthetase(SerRS)promoter-driven dual-luciferase reporter system to screen an in-house library of 384 naturally occurring small molecules and their derivatives to find candidate molecules that could upregulate the expression of SerRS,a potent transcriptional repressor of VEGFA.The levels of SerRS and VEGFA were examined by quantitative RT-PCR(qRT-PCR),western blotting,and/or ELISAs in TNBC cells after candidate molecule administration.Zebrafish,the Matrigel plug angiogenesis assay in mice,the TNBC allograft,and xenograft mouse models were used to evaluate thein vivoanti-angiogenic and anti-cancer activities.Furthermore,the potential direct targets of the candidates were identified by proteomics and biochemical studies.Results:We found the most active compound was 3-(4-methoxyphenyl)quinolin-4(1H)-one(MEQ),an isoflavone derivative.In TNBC cells,MEQ treatment resulted in increased SerRS mRNA(P<0.001)and protein levels and downregulated VEGFA production.Both the vascular development of zebrafish and Matrigel plug angiogenesis in mice were inhibited by MEQ.MEQ also suppressed the angiogenesis in TNBC allografts and xenografts in mice,resulting in inhibited tumor growth and prolonged overall survival(P<0.05).Finally,we found that MEQ regulated SerRS transcription by interacting with MTA2(Metastasis Associated 1 Family Member 2).Conclusions:Our findings suggested that the MTA2/SerRS/VEGFA axis is a drug-treatable anti-angiogenic target,and MEQ is a promising anti-tumor molecule that merits further investigation for clinical applications. | Xiaotong Zhang Gengyi Zou Xiyang Li Lun Wang Tianyu Xie Jin Zhao Longlong Wang Shunchang Jiao Rong Xiang Haoyu Ye Yi Shi | 2020 | Cancer Biology & Medicine2020，17，3： | 6 |
| 2 | Reappraise role of lymph node status in patterns of recurrence following curative resection of gastric adenocarcinoma显示文摘Objective: To examine the association between lymph node status and recurrence patterns in completely resected gastric adenocarcinoma.Methods: We retrospectively assessed 1,694 patients who underwent curative gastrectomy from January 2010 to August 2014. Patients stratified according to lymph node status and recurrence patterns among different subgroups were compared.Results: Of all, 517(30.5%) patients developed recurrent disease, and complete data of recurrence could be obtained in 493(95.4%) patients. For p^(N0) patients, the patterns of recurrence were different according to p T stage: locoregional recurrence was most common in patients with p T1-2 disease(57.1%), distant recurrence was most common in patients with p T3 disease(57.1%), and peritoneal recurrence was most common in patients with p T4 a disease(66.7%). For p^(N+) patients, distant metastasis was most common pattern irrespective of p T stage. The site-specific trend of recurrence showed that locoregional recurrence increased within 5 years in patients with p^(N0)-2 disease but plateaued 3 years after surgery in patients with p N3 disease. Time to recurrence was significantly longer for the p^(N0) patients compared with the p^(N+) patients(median: 25 vs. 16 months, P=0.001).Moreover, post-recurrence survival was significantly better for the p^(N0) patients than for the p^(N+) patients(median:12 vs. 6 months, P<0.001), especially in patients with non-peritoneal recurrence, late recurrence, single recurrence,and receipt of potential curative treatment.Conclusions: Among clinicopathologic factors, lymph node status is the most important factor associated with recurrence patterns after curative gastrectomy. Lymph node status may be used as an adjunct in clinical decisionmaking about postoperative therapeutic and follow-up strategies. | Yihui Tang Jianxian Lin Junpeng Lin Jiabin Wang Jun Lu Qiyue Chen Longlong Caolj Mi Lin Ruhong Tu Changming Huang Ping Li Chaohui Zheng Jianwei Xie | 2021 | Chinese Journal of Cancer Research2021，33，3： | 1 |
| 3 | Drp1-dependent remodeling of mitochondrial morphology triggered by EBV-LMP1 increases cisplatin resistance显示文摘Latent membrane protein 1(LMP1)is a major Epstein–Barr virus(EBV)-encoded oncoprotein involved in latency infection that regulates mitochondrial functions to facilitate cell survival.Recently,mitochondrial fission has been demonstrated as a crucial mechanism in oncovirus-mediated carcinogenesis.Mitochondrial dynamin-related protein 1(Drp1)-mediated mitochondrial fission has an impact on the chemoresistance of cancers.However,the mechanism by which oncogenic stress promotes mitochondrial fission,potentially contributing to tumorigenesis,is not entirely understood.The role of Drp1 in the oncogenesis and prognosis of EBV-LMP1-positive nasopharyngeal carcinoma(NPC)was determined in our study.We show that EBV-LMP1 exhibits a new function in remodeling mitochondrial morphology by activating Drp1.A high level of p-Drp1(Ser616)or a low level of p-Drp1(Ser637)correlates with poor overall survival and disease-free survival.Furthermore,the protein level of p-Drp1(Ser616)is related to the clinical stage(TNM stage)of NPC.Targeting Drp1 impairs mitochondrial function and induces cell death in LMP1-positive NPC cells.In addition,EBV-LMP1 regulates Drp1 through two oncogenic signaling axes,AMPK and cyclin B1/Cdk1,which promote cell survival and cisplatin resistance in NPC.Our findings provide novel insight into the role of EBV-LMP1-driven mitochondrial fission in regulating Drp1 phosphorylation at serine 616 and serine 637.Disruption of Drp1 could be a promising therapeutic strategy for LMP1-positive NPC. | Longlong Xie Feng Shi Yueshuo Li We Li Xinfang Yu Lin Zhao Min Zhou Jianmin Hu Xiangjian Luo Min Tang Jia Fan Jian Zhou Qiang Gao Weizhong Wu Xin Zhang Weihua Liao Ann MBode Ya Cao | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 1 |
| 4 | Correction:Drp1-dependent remodeling of mitochondrial morphology triggered by EBV-LMP1 increases cisplatin resistance显示文摘Correction to:Signal Transduction and Targeted Therapy(2020)5:56,https://doi.org/10.1038/s41392-020-0151-9,published online 20 May 2020 In this article1 an error was noticed in Fig.3d left(p-Drp1 Ser637).The images were misassigned.And one writing error was found in Fig.S1c.The correct figures are given.The authors confirm that these corrections do not change the result interpretation or conclusions of the article. | Longlong Xie Feng Shi Yueshuo Li We Li Xinfang Yu Lin Zhao Min Zhou Jianmin Hu Xiangjian Luo Min Tang Jia Fan Jian Zhou Qiang Gao Weizhong Wu Xin Zhang Weihua Liao Ann M.Bode Ya Cao | 2023 | Signal Transduction and Targeted Therapy2023，8，1： | 0 |
| 5 | Targeting the signaling in Epstein-Barr virus-associated diseases: mechanism, regulation, and clinical study显示文摘Epstein-Barr virus-associated diseases are important global health concerns.As a group I carcinogen,EBV accounts for 1.5%of human malignances,including both epithelial-and lymphatic-originated tumors.Moreover,EBV plays an etiological and pathogenic role in a number of non-neoplastic diseases,and is even involved in multiple autoimmune diseases(SADs).In this review,we summarize and discuss some recent exciting discoveries in EBV research area,which including DNA methylation alterations,metabolic reprogramming,the changes of mitochondria and ubiquitin-proteasome system(UPS),oxidative stress and EBV lytic reactivation,variations in non-coding RNA(ncRNA),radiochemotherapy and immunotherapy.Understanding and learning from this advancement will further confrm the far-reaching and future value of therapeutic strategies in EBV-associated diseases. | Ya Cao Longlong Xie Feng Shi Min Tang Yueshuo Li Jianmin Hu Lin Zha Luqing Zhao Xinfang Yu Xiangjian Luo Weihua Liao Ann MBode | 2021 | Signal Transduction and Targeted Therapy2021，6，2： | 0 |
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