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您的检索式：作者名="Shican Yan"
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| 1 | Insulin-like growth factor 1-induced enolase 2 deacetylation by HDAC3 promotes metastasis of pancreatic cancer显示文摘Enolase 2(ENO2)is a key glycolytic enzyme in the metabolic process of glycolysis,but its potential function in pancreatic ductal adenocarcinoma(PDAC)is unclear.In this study,we observed a significant overexpression of ENO2 in PDAC tissues,and its expression was correlated with metastasis and poor prognosis in PDAC patients.K394 was identified as a major acetylation site in ENO2 that regulates its enzymatic activity,cell metabolism and PDAC progression.Knockdown of ENO2 suppressed tumor growth and liver metastasis in PDAC.Re-expression of wild-type(WT)ENO2,but not the K394 acetylation mimetic mutant,could reverse the decreased tumor malignancy.We further characterized histone deacetylase 3(HDAC3)and P300/CBP-associated factor(PCAF)as the potential deacetylase and acetyltransferase for ENO2,respectively.HDAC3-mediated deacetylation was shown to lead to ENO2 activation and enhancement of glycolysis.Importantly,insulin-like growth factor-1(IGF-1)was found to decrease K394 acetylation and stimulate ENO2 activity in a dose-and time-dependent manner.The PI3K/AKT/mTOR pathway facilitated the phosphorylation of HDAC3 on S424,which promoted K394 deacetylation and activation of ENO2.Linsitinib,an oral small-molecule inhibitor of IGF-1R,could inhibit IGF-1-induced ENO2 deacetylation by HDAC3 and the PI3K/AKT/mTOR pathway.Furthermore,linsitinib showed a different effect on the growth and metastasis of PDAC depending on the overexpression of WT versus K394-mutant ENO2.Our results reveal a novel mechanism by which acetylation negatively regulates ENO2 activity in the metastasis of PDAC by modulating glycolysis.Blockade of IGF-1-induced ENO2 deacetylation represents a promising strategy to prevent the development of PDAC. | Yan Zheng Chao Wu Jimeng Yang Yue Zhao Huliang Jia Min Xue Da Xu Feng Yang Deliang Fu Chaoqun Wang Beiyuan Hu Ze Zhang Tianen Li Shican Yan Xuan Wang Peter J.Nelson Christiane Bruns Lunxiu Qin Qiongzhu Dong | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 3 |
| 2 | miR-345 inhibits migration and stem-like cell phenotype in gastric cancer via inactivation of Rac1 by targeting EPS8显示文摘Tumor metastasis is the main cause of treatment failure and death in patients with late stage of gastric cancer(GC).Studies showed that microRNAs(miRNAs)are important regulators in the process of tumor metastasis.In this study,we used miRNA array analysis to search for metastasisassociated miRNAs in primary and matched metastasis tissues of patients with GC and found that miR-345-5p(miR-345)was significantly higher in primary sites.Decreased expression of miR-345 was observed in GC tissues and cell lines,which was correlated with aggressive stage and grade.Patients with a higher level of miR-345 had a better prognosis,miR-345 could inhibit the migration and spheroid formation abilities in GC cell lines in transwell assay and spheroid formation assay.RNA sequencing and bioinformatics analysis revealed that miR-345 downregulated the epidermal growth factor receptor pathway substrate 8(EPS8)and its downstream Rac1 signaling.Mechanistically,we confirmed that miR-345 could target EPS8 by directly binding to its 3'untranslated region by luciferase reporter assay.Further rescue assay showed that the ability of miR-345 in inhibiting the migration,stem-like cell phenotype,and epithelial-mesenchymal transition(EMT)in GC was partly dependent on targeting EPS8.In conclusion,miR-345 plays an inhibitory role in GC metastasis through inhibiting cell migration,EMT,and cancer stem cell phenotype via inactivation of Rac1 signaling by targeting EPS8,which provides the potential therapeutic and predictive value of miR-345 in GC. | Jieyun Zhang Chenchen Wang Shican Yan Yanan Yang Xiaowei Zhang Weijian Guo | 2020 | Acta Biochimica et Biophysica Sinica2020，52，3： | 3 |
| 3 | Exosomal S100A4 derived from highly metastatic hepatocellular carcinoma cells promotes metastasis by activating STAT3显示文摘Intercellular cross-talk plays important roles in cancer progression and metastasis.Yet how these cancer cells interact with each other is still largely unknown.Exosomes released by tumor cells have been proved to be effective cell-to-cell signal mediators.We explored the functional roles of exosomes in metastasis and the potential prognostic values for hepatocellular carcinoma(HCC).Exosomes were extracted from HCC cells of different metastatic potentials.The metastatic effects of exosomes derived from highly metastatic HCC cells(HMH)were evaluated both in vitro and in vivo.Exosomal proteins were identified with iTRAQ mass spectrum and verified in cell lines,xenograft tumor samples,and functional analyses.Exosomes released by HMH significantly enhanced the in vitro invasion and in vivo metastasis of low metastatic HCC cells(LMH).S100 calcium-binding protein A4(S100A4)was identified as a functional factor in exosomes derived from HMH.S100A4r,ch exosomes significantly promoted tumor metastasis both in vitro and in vivo compared with S100A4^(rich) exosomes or controls.Moreover,exosomal S100A4 could induce expression of osteopontin(OPN),along with other tumor metastasis/stemness-related genes.Exosomal S100A4 activated OPN transcription via STAT3 phosphorylation.HCC patients with high exosomal S100A4 in plasma also had a poorer prognosis.In conclusion,exosomes from HMH could promote the metastatic potential of LMH,and exosomal S100A4 is a key enhancer for HCC metastasis,activating STAT3 phosphorylation and up-regulating OPN expression.This suggested exosomal S100A4 to be a novel prognostic marker and therapeutic target for HCC metastasis. | Haoting Sun Chaoqun Wang Beiyuan Hu Xiaomei Gao Tiantian Zou Qin Luo Mo Chen Yan Fu Yuanyuan Sheng Kaili Zhang Yan Zheng Xudong Ren Shican Yan Yan Geng Luyu Yang Qiongzhu Dong Lunxiu Qin | 2021 | Signal Transduction and Targeted Therapy2021，6，6： | 1 |
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