|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | RAB31 marks and controls an ESCRT-independent exosome pathway显示文摘Exosomes are generated within the multivesicular endosomes(MVEs)as intraluminal vesicles(ILVs)and secreted during the fusion of MVEs with the cell membrane.The mechanisms of exosome biogenesis remain poorly explored.Here we identify that RAB31 marks and controls an ESCRT-independent exosome pathway.Active RAB31,phosphorylated by epidermal growth factor receptor(EGFR),engages flotillin proteins in lipid raft microdomains to drive EGFR entry into MVEs to form ILVs,which is independent of the ESCRT(endosomal sorting complex required for transport)machinery.Active RAB31 interacts with the SPFH domain and drives ILV formation via the Flotillin domain of flotillin proteins.Meanwhile,RAB31 recruits GTPase-activating protein TBC1D2B to inactivate RAB7,thereby preventing the fusion of MVEs with lysosomes and enabling the secretion of ILVs as exosomes.These findings establish that RAB31 has dual functions in the biogenesis of exosomes:driving ILVs formation and suppressing MVEs degradation,providing an exquisite framework to better understand exosome biogenesis. | Denghui Wei Weixiang Zhan Ying Gao Liyan Huang Run Gong Wen Wang Ruhua Zhang Yuanzhong Wu Song Gao Tiebang Kang | 2021 | Cell Research2021，31，2： | 12 |
| 2 | Identification of immune cell infiltration landscape for predicting prognosis of colorectal cancer显示文摘Background:The tumor microenvironment plays an essential role in the therapeutic response to immunotherapy.It is necessary to identify immune cell infiltration(ICI)subtypes for evaluating prognosis and therapeutic benefits.This study aimed to evaluate the ICI score as an effective prognostic biomarker for immune response.Methods:The cell-type identification by estimating relative subsets of RNA transcripts and the estimation of stromal and immune cells in malignant tumors using expression methods were used to analyse ICI landscapes in 161 colorectal cancer(CRC)samples with patients’clinical and prognostic data,RNA sequencing data,and whole-exome sequencing data from the Sixth Affiliated Hospital,Sun Yat-sen University(Guangzhou,China).Statistical analysis and data processing were conducted to calculate ICI scores,and to analyse the prognosis of CRC patients with different ICI scores and other features.A similar analysis with RNA sequencing and clinical data of colon adenocarcinoma(COAD)samples from The Cancer Genome Atlas(TCGA)database was conducted to confirm the correctness of the findings.Results:The high-ICI score group with a better prognosis(hazard ratio[HR],2.19;95%confidence interval[CI],1.03–4.64;logrank test,P=0.036)was characterized by the increased tumor mutational burden and interleukin-17(IL-17)signaling pathway.Significant differences in the prognosis and the expression levels of immune checkpoints and chemokine marker genes were found between the two ICI score groups.For COAD samples from TCGA,the results also showed a significant difference in patients’prognosis between the two ICI score groups(HR,1.72;95%CI,1.00–2.96;log-rank test,P=0.047).Conclusions:Tumor heterogeneity induced differences in identifying ICI subtypes of CRC patients.The ICI score may serve as an effective biomarker for predicting prognosis,help identify new therapeutic markers for CRC,and develop novel effective immune checkpoint blockade therapies. | Xueqian Wu Jianxia Li Yuanzhe Zhang Yi Cheng Zehua Wu Weixiang Zhan Yanhong Deng | 2023 | Gastroenterology Report2023，11，1： | 1 |
| 3 | Pharmacological inhibition of BAP1 recruits HERC2 to competitively dissociate BRCA1-BARD1, suppresses DNA repair and sensitizes CRC to radiotherapy显示文摘Radiotherapy is widely used in the management of advanced colorectal cancer(CRC).However,the clinical efficacy is limited by the safe irradiated dose.Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation.The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination(HR)DSB repair,and its functions may be affected by HERC2 or BAP1.Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes;however,the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn’t been defined.Through activity-based profiling,we identified PT33 as an active entity for HR repair suppression.Subsequently,we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen.Mechanistically,pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction,interrupting HR repair.Consequently,PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo.Overall,these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain. | Xin Yue Tingyu Liu Xuecen Wang Weijian Wu Gesi Wen Yang Yi Jiaxin Wu Ziyang Wang Weixiang Zhan Ruirui Wu Yuan Meng Zhirui Cao Liyuan Le Wenyan Qiu Xiaoyue Zhang Zhenyu Li Yong Chen Guohui Wan Xianzhang Bu Zhenwei Peng Ran-yi Liu | 2023 | Acta Pharmaceutica Sinica B2023，13，8： | 1 |
| 4 | Intercellular transfer of activated STING triggered by RAB22A-mediated non-canonical autophagy promotes antitumor immunity显示文摘STING,an endoplasmic reticulum(ER)transmembrane protein,mediates innate immune activation upon cGAMP stimulation and is degraded through autophagy.Here,we report that activated STING could be transferred between cells to promote antitumor immunity,a process triggered by RAB22A-mediated non-canonical autophagy.Mechanistically,RAB22A engages PI4K2A to generate PI4P that recruits the Atg12–Atg5–Atg16L1 complex,inducing the formation of ER-derived RAB22A-mediated non-canonical autophagosome,in which STING activated by agonists or chemoradiotherapy is packaged.This RAB22A-induced autophagosome fuses with RAB22A-positive early endosome,generating a new organelle that we name Rafeesome(RAB22A-mediated non-canonical autophagosome fused with early endosome).Meanwhile,RAB22A inactivates RAB7 to suppress the fusion of Rafeesome with lysosome,thereby enabling the secretion of the inner vesicle of the autophagosome bearing activated STING as a new type of extracellular vesicle that we define as R-EV(RAB22A-induced extracellular vesicle).Activated STING-containing R-EVs induce IFNβrelease from recipient cells to the tumor microenvironment,promoting antitumor immunity.Consistently,RAB22A enhances the antitumor effect of the STING agonist diABZI in mice,and a high RAB22A level predicts good survival in nasopharyngeal cancer patients treated with chemoradiotherapy.Our findings reveal that Rafeesome regulates the intercellular transfer of activated STING to trigger and spread antitumor immunity,and that the inner vesicle of non-canonical autophagosome originated from ER is secreted as R-EV,providing a new perspective for understanding the intercellular communication of organelle membrane proteins. | Ying Gao Xueping Zheng Boyang Chang Yujie Lin Xiaodan Huang Wen Wang Shirong Ding Weixiang Zhan Shang Wang Beibei Xiao Lanqing Huo Youhui Yu Yilin Chen Run Gong Yuanzhong Wu Ruhua Zhang Li Zhong Xin Wang Qiuyan Chen Song Gao Zhengfan Jiang Denghui Wei Tiebang Kang | 2022 | Cell Research2022，32，12： | 1 |
| 5 | RMI2 plays crucial roles in growth and metastasis of lung cancer显示文摘Dear Editor,Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in the world,but its therapeutic targets are still being explored.Genome instability as a key hallmark of cancer not only contributes to cancer initiation and progression,1 but also creates vulnerabilities that are relatively specific to cancer cells,which may be potential therapeutic targets for cancer patients.During DNA Double-Strand Breaks(DSBs)repair,BTR(BLM-Topo IIIα-RMI1/RMI2)complex promotes the dissolution of double Holliday junctions to form non-crossover products and is often considered as a tumor suppressor.2 However,the function of each individual component of this BTR complex in cancer remains largely unknown. | Weixiang Zhan Yina Liu Ying Gao Run Gong Wen Wang Ruhua Zhang Yuanzhong Wu Tiebang Kang Denghui Wei | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 0 |
您所在的机构暂未开通此部分的功能，请联系管理员