|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Josephin domain containing 2(JOSD2)promotes lung cancer by inhibiting LKB1(Liver kinase B1)activity显示文摘Non-small cell lung cancer(NSCLC)ranks as one of the leading causes of cancer-related deaths worldwide.Despite the prominence and effectiveness of kinase-target therapies in NSCLC treatment,these drugs are suitable for and beneficial to a mere~30%of NSCLC patients.Consequently,the need for novel strategies addressing NSCLC remains pressing.Deubiquitinases(DUBs),a group of diverse enzymes with well-defined catalytic sites that are frequently overactivated in cancers and associated with tumorigenesis and regarded as promising therapeutic targets.Nevertheless,the mechanisms by which DUBs promote NSCLC remain poorly understood.Through a global analysis of the 97 DUBs’contribution to NSCLC survival possibilities using The Cancer Genome Atlas(TCGA)database,we found that high expression of Josephin Domain-containing protein 2(JOSD2)predicted the poor prognosis of patients.Depletion of JOSD2 significantly impeded NSCLC growth in both cell/patient-derived xenografts in vivo.Mechanically,we found that JOSD2 restricts the kinase activity of LKB1,an important tumor suppressor generally inactivated in NSCLC,by removing K6-linked polyubiquitination,an action vital for maintaining the integrity of the LKB1-STRAD-MO25 complex.Notably,we identified the first small-molecule inhibitor of JOSD2,and observed that its pharmacological inhibition significantly arrested NSCLC proliferation in vitro/in vivo.Our findings highlight the vital role of JOSD2 in hindering LKB1 activity,underscoring the therapeutic potential of targeting JOSD2 in NSCLC,especially in those with inactivated LKB1,and presenting its inhibitors as a promising strategy for NSCLC treatment. | Tao Yuan Chenming Zeng Jiawei Liu Chenxi Zhao Fujing Ge Yuekang Li Meijia Qian Jiamin Du Weihua Wang Yonghao Li Yue Liu Xiaoyang Dai Jianya Zhou Xueqin Chen Shenglin Ma Hong Zhu Qiaojun He Bo Yang | 2024 | Signal Transduction and Targeted Therapy2024，9，2： | 0 |
| 2 | CIS controls the functional polarization of GM-CSF-derived macrophages显示文摘The cytokine granulocyte-macrophage-colony stimulating factor (GM-CSF) possesses the capacity to differentiate monocytes into macrophages (MØs) with opposing functions, namely, proinflammatory M1-like MØs and immunosuppressive M2-like MØs. Despite the importance of these opposing biological outcomes, the intrinsic mechanism that regulates the functional polarization of MØs under GM-CSF signaling remains elusive. Here, we showed that GM-CSF-induced MØ polarization resulted in the expression of cytokine-inducible SH2-containing protein (CIS) and that CIS deficiency skewed the differentiation of monocytes toward immunosuppressive M2-like MØs. CIS deficiency resulted in hyperactivation of the JAK-STAT5 signaling pathway, consequently promoting downregulation of the transcription factor Interferon Regulatory Factor 8 (IRF8). Loss- and gain-of-function approaches highlighted IRF8 as a critical regulator of the M1-like polarization program. In vivo, CIS deficiency induced the differentiation of M2-like macrophages, which promoted strong Th2 immune responses characterized by the development of severe experimental asthma. Collectively, our results reveal a CIS-modulated mechanism that clarifies the opposing actions of GM-CSF in MØ differentiation and uncovers the role of GM-CSF in controlling allergic inflammation. | Shengbo Zhang Jai Rautela Naiara G.Bediaga Tatiana B.Kolesnik Yue You Junli Nie Laura F.Dagley Justin Bedo Hanqing Wang Li Sun Robyn Sutherland Elliot Surgenor Nadia Iannarella Rhys Allan Fernando Souza-Fonseca-Guimaraes Yi Xie Qike Wang Yuxia Zhang Yuekang Xu Stephen L.Nutt Andrew M.Lew Nicholas D.Huntington Sandra E.Nicholson Michaël Chopin Yifan Zhan | 2023 | Cellular & Molecular Immunology2023，20，1： | 0 |
| 3 | Exposing vertebral artery from lateral to medial under the guide of peri-vertebral artery fat pad in far lateral approach显示文摘Far lateral approach(FLA),together with its modified approaches,is a fundamental surgical approach for surgical resection of lesions located at the ventral or ventrolateral side of the foramen magnum.[1,2,3,4,5]The key procedure in FLA is exposing the vertebral artery(VA)especially the V3 segment.[1,5,6]When performing an FLA,most neurosurgeons choose to expose the suboccipital triangle(formed by the rectus capitis posterior major,the superior oblique,and the inferior oblique)as a key anatomical landmark initially and then expose the V3 segment.[1,2,5,6,7]However,on the one hand,this muscular anatomical landmarks-suboccipital triangle varies in depth,morphology,and location in different patients,which increases the risk of VA injury during surgery.[3]On the other hand,this procedure could lead to exposing difficulty due to the obstruction of overlying layers of muscles and the distribution of blood vessels,which could prolong the time for craniotomy fairly.The course of VA could vary,such as looping backward and bulge posteriorly between the lips of the suboccipital triangle,where it could be damaged if one expects it to be found in the depth of the suboccipital triangle.[3]Thus,neurosurgeons have the potential for VA injury and a rather prolonged time to successfully expose VA. | Jiuhong Li Linlin Song Zhigang Lan Wenke Liu Yuekang Zhang Xuhui Hui Jianguo Xu Xuesong Liu | 2022 | Chinese Medical Journal2022，，4： | 0 |
您所在的机构暂未开通此部分的功能，请联系管理员