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| 1 | The zinc transporter Slc39a5 controls glucose sensing and insulin secretion in pancreatic β-cells via Sirt1- and Pgc-1α-mediated regulation of Glut2显示文摘Zinc levels are high in pancreatic β-cells, and zinc is involved in the synthesis, processing and secretion of insulin in these cells. However, precisely how cellular zinc homeostasis is regulated in pancreatic β-cells is poorly understood. By screening the expression of 14 Slc39a metal importer family member genes, we found that the zinc transporter Slc39a5 is significantly downregulated in pancreatic β-cells in diabetic db/db mice, obese ob/ob mice and high-fat diet-fed mice. Moreover,β-cell-specific Slc39a5 knockout mice have impaired insulin secretion. In addition, Slc39a5-deficient pancreatic islets have reduced glucose tolerance accompanied by reduced expression of Pgc-1α and its downstream target gene Glut2. The down-regulation of Glut2 in Slc39a5-deficient islets was rescued using agonists of Sirt1, Pgc-1α and Ppar-γ. At the mechanistic level, we found that Slc39a5-mediated zinc influx induces Glut2 expression via Sirt1-mediated Pgc-1α activation. These findings suggest that Slc39a5 may serve as a possible therapeutic target for diabetes-related conditions. | Xinhui Wang Hong Gao Wenhui Wu Enjun Xie Yingying Yu Xuyan He Jin Li Wanru Zheng Xudong Wang Xizhi Cao Zhuoxian Meng Ligong Chen Junxia Min Fudi Wang | 2019 | Protein & Cell2019，10，6： | 6 |
| 2 | The structure of erastin-bound xCT-4F2hc complex reveals molecular mechanisms underlying erastin-induced ferroptosis显示文摘Dear Editor,Ferroptosis is an iron-dependent,non-apoptotic form of regulated cell death characterized by an accumulation of lipid.derived reactive oxygen species(ROS).The small-molecule compo und erastin in duces ferroptosis via in hibiti ng the cystineglutamate antiporter system x_(c).which consists of two subunits,namely the light chain xCT and the heavy chain 4F2hc(encoded by the SLC7A11 and SLC3A2 genes,respectively).^(1-4) | Renhong Yan Enjun Xie Yaning Li Jin Li Yuanyuan Zhang Ximin Chi Xueping Hu Lei xu Tingjun Hou Brent R.Stockwell Junxia Min Qiang Zhou Fudi Wang | 2022 | Cell Research2022，32，7： | 4 |
| 3 | Rewiring ERBB3 and ERK signaling confers resistance to FGFR1 inhibition in gastrointestinal cancer harbored an ERBB3-E928G mutation显示文摘Dear Editor,Recently,a large number of studies found that activation of ERBB3(Erb-B2 receptor tyrosine kinase 3,also known as HER3)may be one of the major mechanisms underlying resistance to therapies that target the EGFR(epidermal growth factor receptor),HER2,and other receptor tyrosine kinases(RTKs)(Chen et al.,2011;Choi et al.,2012;Ross et al.,2018).Interestingly,mutations in ERBB3 are commonly reported in gastrointestinal(Gl)cancer,with mutations identified in approximately 12%of stomach and colorectal cancer cases(Jaiswal et al.,2013). | Xiang Yang Hongxiao Wang Enjun Xie Biyao Tang Qingdian Mu Zijun Song Junyi Chen Fudi Wang Junxia Min | 2020 | Protein & Cell2020，11，12： | 1 |
| 4 | Targeting the LSD1-G9a-ER Stress Pathway as a Novel Therapeutic Strategy for Esophageal Squamous Cell Carcinoma显示文摘Despite recent advances in the management and treatment of esophageal squamous cell carcinoma(ESCC),the prognosis remains extremely poor,and current nonsurgical treatment options are limited.To identify new therapeutic targets,we screened a curated library of epigenetic compounds using a panel of cancer cell lines and found that coinhibiting the histone demethylase LSD1 and the histone methyltransferase G9a potently suppresses cell growth;similar results were obtained by knocking down both LSD1 and G9a expression.Importantly,we also found that inhibiting LSD1 and G9a significantly decreased tumor growth in a xenograft mouse model with ESCC cell lines.To examine the clinical relevance of these findings,we performed immunohistochemical analyses of microarray profiling data obtained from human esophageal squamous cancer tissues and found that both LSD1 and G9a are upregulated in cancer tissues compared to healthy tissues,and this increased expression was significantly correlated with poor prognosis.Mechanistically,we discovered that inhibiting LSD1 and G9a induces cell death via S-phase arrest and apoptosis,and cotargeting ER stress pathways increased this effect both in vitro and in vivo.Taken together,these findings provide compelling evidence that targeting LSD1,G9a,and ER stress-related pathways may serve as a viable therapeutic strategy for ESCC. | Hongxiao Wang Zijun Song Enjun Xie Junyi Chen Biyao Tang Fudi Wang Junxia Min | 2022 | Research2022，，3： | 0 |
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