更新于：2024-09-19

RPS6KB2

更新于：2024-09-19

基本信息

别名

70 kDa ribosomal protein S6 kinase 2、KLS、p70 ribosomal S6 kinase beta

+ [21]

简介

Phosphorylates specifically ribosomal protein S6 (PubMed:29750193). Seems to act downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression in an alternative pathway regulated by MEAK7 (PubMed:29750193).

关联

100 项与 RPS6KB2 相关的临床结果

登录后查看更多信息

100 项与 RPS6KB2 相关的转化医学

登录后查看更多信息

0 项与 RPS6KB2 相关的专利（医药）

登录后查看更多信息

265

项与 RPS6KB2 相关的文献（医药）

2024-12-01·Molecular Biology Reports

Ribosomal protein S6 kinase 2 (RPS6KB2) is a potential immunotherapeutic target for cancer that upregulates proinflammatory cytokines

Article

作者: Hao, Jiqing ; Gong, Peng ; Ma, Qiang ; Chen, Shuwen ; Cheng, Hao ; Yang, Yipin

BACKGROUNDCancer is still a leading cause of mortality. Over the years, cancer therapy has undergone significant advances driven by advancements in science and technology. A promising area of drug discovery in this field involves the development of therapeutic targets for cancer treatment. The urgent need to identify new pharmacological targets arises from the impact of tumor resistance on the effectiveness of current medications. Specifically, the RPS6KB2 gene on chromosome 11 has been implicated in cell cycle regulation and exhibits higher expression levels in tumor tissue. Given this association, there is a potential for this gene to serve as a target for cancer treatment.METHODSWe conducted an analysis using the GTEx, TCGA, and CCLE databases to explore the relationship between RPS6KB2 and immune infiltration, the tumor microenvironment (TME), microsatellite instability (MSI), and more. Cell proliferation was assessed using EDU detection, while cell invasion and migration were evaluated via wound healing and Transwell assays. Additionally, western blot analysis was employed to measure expression of Bax, Bcl-2, MMP2, MMP9, PCNA, and proinflammatory factors.RESULTSThrough data analysis and molecular biology methods, our study carefully examined the potential role of RPS6KB2 in cancer therapy. The data revealed that RPS6KB2 is aberrantly expressed in most cancers and is associated with poor prognosis. Further analysis indicated its involvement in cancer cell apoptosis and migration, as well as its role in cancer immune processes. We validated the significance of RPS6KB2 in hepatocellular carcinoma (HCC), highlighting its capacity to upregulate proinflammatory cytokines.CONCLUSIONOur research indicates that RPS6KB2 is a prognostic biomarker associated with immune infiltration in cancer that can affect antitumor immunity by increasing secretion of proinflammatory factors, providing a potential drug target for cancer treatment.

2024-09-01·BIT Numerical Mathematics

From low-rank retractions to dynamical low-rank approximation and back

Article

作者: Kressner, Daniel ; Séguin, Axel ; Ceruti, Gianluca

AbstractIn algorithms for solving optimization problems constrained to a smooth manifold, retractions are a well-established tool to ensure that the iterates stay on the manifold. More recently, it has been demonstrated that retractions are a useful concept for other computational tasks on manifold as well, including interpolation tasks. In this work, we consider the application of retractions to the numerical integration of differential equations on fixed-rank matrix manifolds. This is closely related to dynamical low-rank approximation (DLRA) techniques. In fact, any retraction leads to a numerical integrator and, vice versa, certain DLRA techniques bear a direct relation with retractions. As an example for the latter, we introduce a new retraction, called KLS retraction, that is derived from the so-called unconventional integrator for DLRA. We also illustrate how retractions can be used to recover known DLRA techniques and to design new ones. In particular, this work introduces two novel numerical integration schemes that apply to differential equations on general manifolds: the accelerated forward Euler (AFE) method and the Projected Ralston–Hermite (PRH) method. Both methods build on retractions by using them as a tool for approximating curves on manifolds. The two methods are proven to have local truncation error of order three. Numerical experiments on classical DLRA examples highlight the advantages and shortcomings of these new methods.

2024-08-01·Cancer Research Communications

Coordinated Targeting of S6K1/2 and AXL Disrupts Pyrimidine Biosynthesis in PTEN-Deficient Glioblastoma

Article

作者: Von Handorf, Kate M ; Sengupta, Soma ; Plas, David R. ; Wetzel, Collin ; Andreani, Cristina ; Kendler, Ady ; Sarkaria, Jann N. ; Clark, Nicholas A ; Qi, Xiaoyang ; Sarma, Pranjal ; Clark, Nicholas A. ; Ennis, Kelli N. ; Behrmann, Catherine A. ; Sarkaria, Jann N ; Meller, Jarek ; Ennis, Kelli N ; Von Handorf, Kate M. ; Behrmann, Catherine A ; Scaglioni, Pier Paolo ; Dasgupta, Biplab ; Medvedovic, Mario ; Plas, David R ; Czyzyk-Krzeska, Maria F. ; Vallabhapurapu, Subrahmanya ; Czyzyk-Krzeska, Maria F ; Reigle, James

AbstractIntrinsic resistance to targeted therapeutics in PTEN-deficient glioblastoma (GBM) is mediated by redundant signaling networks that sustain critical metabolic functions. Here, we demonstrate that coordinated inhibition of the ribosomal protein S6 kinase 1 (S6K1) and the receptor tyrosine kinase AXL using LY-2584702 and BMS-777607 can overcome network redundancy to reduce GBM tumor growth. This combination of S6K1 and AXL inhibition suppressed glucose flux to pyrimidine biosynthesis. Genetic inactivation studies to map the signaling network indicated that both S6K1 and S6K2 transmit growth signals in PTEN-deficient GBM. Kinome-wide ATP binding analysis in inhibitor-treated cells revealed that LY-2584702 directly inhibited S6K1, and substrate phosphorylation studies showed that BMS-777607 inactivation of upstream AXL collaborated to reduce S6K2-mediated signal transduction. Thus, combination targeting of S6K1 and AXL provides a kinase-directed therapeutic approach that circumvents signal transduction redundancy to interrupt metabolic function and reduce growth of PTEN-deficient GBM.Significance:Therapy for glioblastoma would be advanced by incorporating molecularly targeted kinase-directed agents, similar to standard of care strategies in other tumor types. Here, we identify a kinase targeting approach to inhibit the metabolism and growth of glioblastoma.

项与 RPS6KB2 相关的新闻（医药）

2022-07-19

·药时代

iPS干细胞治疗糖尿病，竟导致患者出现肿瘤？

2006年，日本京都大学山中伸弥教授在 Cell 期刊发表论文，发现将 Oct3/4、Sox2、Klf4、c-Myc 这四种转录因子通过病毒载体导入成熟体细胞后，可将体细胞转化为诱导多能干细胞（iPSC）。山中伸弥因此获得了2012年诺贝尔生理学或医学奖，也开启了 iPSC 治疗的新时代。近年来，基于 iPSC 的 CAR-T、CAR-NK 细胞疗法，以及再生医学和抗衰老研究如火如荼。然而，诱导的 iPSC 可能存在细胞过度生长和癌变风险，因此具有潜在致癌性。早在2009年，山中伸弥就曾在 Nature Biotechnology 期刊发表论文，显示胚胎成纤维细胞来源的 iPS 神经干细胞植入小鼠后，具有较高的成瘤风险。近日，Stem Cells and Development 期刊发表了一篇题为：Distinctive Clinical and Pathologic Features of Immature Teratomas Arising from Induced Pluripotent Stem Cell-Derived Beta Cell Injection in a Diabetes Patient 的论文。尽管目前有许多基于 iPSC 的细胞疗法的临床试验，但仍不清楚是否会在患者中发生真正的肿瘤。这篇论文报告了第一例 iPSC 来源细胞治疗2型糖尿病后形成未成熟畸胎瘤的临床病例。与成熟畸胎瘤不同，未成熟畸胎瘤具有复发和转移的潜力，论文作者强调，在使用 iPSC 细胞治疗时，应当更加关注畸胎瘤的形成，并进一步探索治疗的安全性和有效性。糖尿病是一种以高血糖、胰岛素抵抗和血糖调节缺陷为特征的代谢性疾病，可损害各种器官功能。据WHO预测，到2030年，全球糖尿病患者人数将翻一番，造成严重的社会经济负担。2型糖尿病（T2DM）占所有糖尿病病例的85%-95%，其特征是胰岛素抵抗和胰腺β细胞的胰岛素分泌受损，多数患者需要终生接受胰岛素注射来控制血糖，这常导致不可逆胰腺β细胞损伤并引起严重并发症。近年来，越来越多的研究开始聚焦于使用人诱导多能干细胞（hiPSC）来源的β细胞来治疗胰岛中不可逆的β细胞损伤，并被认为是治愈糖尿病的有潜力的方法。然而，iPSC 的致瘤性一定程度上阻碍了其临床应用，在体外和体内 iPSC 实验模型中，已检测到其存在广泛的基因组不稳定性，包括染色体畸变、拷贝数变异和单核苷酸变异等，小鼠模型实验也观察到了存在致瘤性，此外，还有少数临床试验病例报道了 iPSC 来源的细胞在移植后形成肿瘤或肿瘤样病变。但目前还没有 iPSC 治疗2型糖尿病后导致患者出现肿瘤的病例报道。这篇论文报道了一例2型糖尿病患者在接受 iPSC 来源细胞治疗后形成未成熟畸胎瘤的病例。该2型糖尿病患者接受移植的β细胞是由自体 iPSC 分化而来，2020年6月，该患者在北京的某家医院接受了自体 iPSC 来源的β细胞的注射，病历显示，该患者血液中分离的体细胞被重编程为 iPSC，然后再分化为胰岛β细胞，在扩增后通过左上臂的三角肌注射到患者体内。到治疗后2个月，患者的血糖调节和胰岛素水平并没有改善，反而在注射位置出现肿块以及腋窝淋巴结肿大。此后，这名患者来到了云南省肿瘤医院接受了治疗（该患者的iPSC治疗并非在云南省肿瘤医院进行）。磁共振成像（MRI）扫描提示，该肿瘤为良性或中间性肿瘤。2020年8月，患者接受了肿瘤切除手术，病理诊断显示是未成熟畸胎瘤。PET-CT 检查显示存在同侧腋窝和颈部淋巴结转移。经过两个周期的常规化疗后，患者的肿瘤出现进展。此后患者接受了颈部和腋窝手术区的辅助放疗，并结合化疗。到2021年10月，PET-CT 显示患者没有出现肿瘤复发或远端转移。为了确定畸胎瘤中是否存在胰岛β细胞，通过免疫荧光测定检测诱导的 iPSC 的关键标志物 OCT4 和 SOX2 基因表达，二者在细胞核或细胞质中均呈阳性。然而，对肿瘤细胞中胰岛素的免疫组织化学染色呈阴性。OCT4 和 SOX2 阳性，表明注射后的细胞并未完全分化。而胰岛素阴性表明这些细胞没有产生胰岛素分泌功能，这说明 iPSC 在体外诱导的状态不代表在体内植入后的状态。对患者的肿瘤组织进行的高通量测序显示，患者肿瘤细胞中存在 ABCB4、CDC73、CROT、DNMT3A、HCK、KMT2D、MSH2、MSH6、NCOR2、PRDM1、PREX2、RPS6KB2、TRAF7、ZFHX3、ZNF703 和 ZRSR2 这16个基因的错义或移码突变。iPSC 来源的细胞疗法已经在临床试验中显示了对癌症、神经图形学疾病以及糖尿病的疗效。与其他干细胞疗法相比，iPSC 细胞具有更易获取、扩增迅速、免疫原性低、无伦理问题等显著优势。然而，基于 iPSC 的细胞治疗具有致瘤性的潜在风险，这是其在推广到临床过程中面临的一大障碍。越来越多的证据表明，iPSC 的重编程会带来潜在致瘤性风险，例如病毒载体带来的基因插入、转录因子的长期过表达等等。2022年4月，Altos Labs 公司在 Nature Aging 发表的一项研究显示【2】，通过瞬时表达重编程因子（Oct4、Sox2、Klf4 和 c-Myc）对衰老小鼠进行体内重编程，恢复了衰老细胞的年轻表观遗传特征，并延长了早衰小鼠模型寿命。这提示了我们，瞬时诱导方案效果良好，且没有观察到致瘤性等潜在副作用。最后，论文作者总结道，在 iPSC 来源的β细胞治疗糖尿病后，应更加关注畸胎瘤的形成，因为形成的未成熟畸胎瘤比典型的成熟畸胎瘤更具侵袭性。应在标准临床试验中进一步探索 iPSC 来源细胞治疗糖尿病的安全性和有效性。论文链接：1.https://www.liebertpub.com/doi/10.1089/scd.2021.02552.https://www.nature.com/articles/s43587-022-00183-2版权声明/免责声明本文为授权转载文章，版权归拥有者。仅供感兴趣的个人谨慎参考，非商用，非医用、非投资用。欢迎朋友们批评指正！衷心感谢！文中图片、视频为授权正版作品，或来自微信公共图片库，或取自公司官网/网络根据CC0协议使用，版权归拥有者。任何问题，请与我们联系（电话：13651980212。微信：27674131。邮箱：contact@drugtimes.cn）。衷心感谢！推荐阅读首款国产新冠中和抗体，不仅是抗疫的新助力，更是新药研发成功的经典案例...重磅信号！四环医美+生物医药双轮驱动战略迈出坚实步伐热烈祝贺「中国肝病新药联盟」成立！新一届组委会诞生！智慧芽创始人、CEO张济徽：生物医药，智慧芽笃定的未来黎健博士 | 生子当如布鲁斯！——诺贝尔奖得主Bruce Beutler教授的故事热烈祝贺《中国药理学报》「NASH专刊」出版！十多位专家分享真知灼见，中国NASH新药联盟和药时代全力协助PD-1出海接力赛：FDA官网更新了「7月12日批准」的药物名单，没有百济神州...Moderna突破Moderna！变革从新品牌、新Logo开始。。。沙利文发布《眼科药物市场发展现状与未来趋势研究报告》（内附完整报告获取方式）如何解读反弹后稳住的恒瑞医药当出海已经关乎药企的「生与死」，我们还能如何寻求助力？| 药时代出海系列阿尔茨海默病：何以解忧，唯有新药集采第七轮来临，恒瑞业绩拐点究竟何在？2100万美元收购！Portage Biotech全力以赴地投身于腺苷通路点击这里，欢聚药时代！

细胞疗法抗体免疫疗法并购放射疗法