keyword
MENU ▼
Read by QxMD icon Read
search

rictor

keyword
https://www.readbyqxmd.com/read/29755672/inhibition-of-mtor-complex-2-restrains-tumor-angiogenesis-in-multiple-myeloma
#1
Aurelia Lamanuzzi, Ilaria Saltarella, Vanessa Desantis, Maria Antonia Frassanito, Patrizia Leone, Vito Racanelli, Beatrice Nico, Domenico Ribatti, Paolo Ditonno, Marcella Prete, Antonio Giovanni Solimando, Francesco Dammacco, Angelo Vacca, Roberto Ria
The mammalian Target of Rapamycin (mTOR) is an intracellular serine/threonine kinase that mediates intracellular metabolism, cell survival and actin rearrangement. mTOR is made of two independent complexes, mTORC1 and mTORC2, activated by the scaffold proteins RAPTOR and RICTOR, respectively. The activation of mTORC1 triggers protein synthesis and autophagy inhibition, while mTORC2 activation promotes progression, survival, actin reorganization, and drug resistance through AKT hyper-phosphorylation on Ser473...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29621478/hyperglycemia-induced-bcl-2-bax-mediated-apoptosis-of-schwann-cells-via-mtorc1-s6k1-inhibition-in-diabetic-peripheral-neuropathy
#2
Lin Zhu, Jun Hao, Meijuan Cheng, Cuihong Zhang, Chunxiu Huo, Yaping Liu, Wei Du, Xianghong Zhang
Schwann cell apoptosis is one of the characteristics of diabetic peripheral neuropathy (DPN). The mammalian target of rapamycin (mTOR) is a multifunctional signaling pathway that regulates cell apoptosis in various types of tissues and cells. To investigate whether the mTOR pathway is involved in cell apoptosis in the Schwann cells of DPN, diabetic mice and rat Schwann cells (RSC96) were chosen to detect phospho-mTOR (Ser 2448), phospho-S6K1 (Thr 389), phospho-4EBP1 (Thr 37/46), Bcl-2, Bax and cleaved caspase-3 by diverse pathological and biological techniques...
June 15, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29617677/the-mtor-kinase-inhibitor-cz415-inhibits-human-papillary-thyroid-carcinoma-cell-growth
#3
Xiaobin Li, Zongze Li, Yimin Song, Wenjing Liu, Ziwen Liu
BACKGROUND/AIM: Mammalian target of rapamycin (mTOR) plays an important role in papillary thyroid carcinoma (PTC) cell progression. CZ415 is a novel, highly-efficient and specific mTOR kinase inhibitor. The current study tested the potential anti-tumor activity of CZ415 in human PTC cells. METHODS: The established (TPC-1 cell line) and primary human PTC cells were treated with CZ415. Cell survival and growth were tested by Cell Counting Kit-8 assay and BrdU ELISA assay, respectively...
March 28, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29581766/large-intergenic-non-coding-rna-ror-inhibits-aerobic-glycolysis-of-glioblastoma-cells-via-akt-pathway
#4
Yong Li, Zhi-Cheng He, Qing Liu, Kai Zhou, Yu Shi, Xiao-Hong Yao, Xia Zhang, Hsiang-Fu Kung, Yi-Fang Ping, Xiu-Wu Bian
Reprogramming energy metabolism is a hallmark of malignant tumors, including glioblastoma (GBM). Aerobic glycolysis is often utilized by tumor cells to maintain survival and proliferation. However, the underlying mechanisms of aerobic glycolysis in GBM remain elusive. Herein, we demonstrated that large intergenic non-coding RNA-RoR (LincRNA-RoR) functioned as a critical suppressor to inhibit the aerobic glycolysis and viability of GBM cells. We found that LincRNA-RoR was markedly reduced in GBM tissues compared with adjacent non-tumor tissues from 10 cases of GBM patients...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29575816/kidney-derived-c-kit-cells-possess-regenerative-potential
#5
Samirah A Gomes, Joshua M Hare, Erika B Rangel
Kidney-derived c-Kit+ cells exhibit progenitor/stem cell properties in vitro (self-renewal capacity, clonogenicity, and multipotentiality). These cells can regenerate epithelial tubular cells following ischemia-reperfusion injury and accelerate foot processes effacement reversal in a model of acute proteinuria in rats. Several mechanisms are involved in kidney regeneration by kidney-derived c-Kit+ cells, including cell engraftment and differentiation into renal-like structures, such as tubules, vessels, and podocytes...
April 2018: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29567957/cryo-em-structure-of-human-mtor-complex-2
#6
Xizi Chen, Mengjie Liu, Yuan Tian, Jiabei Li, Yilun Qi, Dan Zhao, Zihan Wu, Min Huang, Catherine C L Wong, Hong-Wei Wang, Jiawei Wang, Huirong Yang, Yanhui Xu
Mechanistic target of rapamycin (mTOR) complex 2 (mTORC2) plays an essential role in regulating cell proliferation through phosphorylating AGC protein kinase family members, including AKT, PKC and SGK1. The functional core complex consists of mTOR, mLST8, and two mTORC2-specific components, Rictor and mSin1. Here we investigated the intermolecular interactions within mTORC2 complex and determined its cryo-electron microscopy structure at 4.9 Å resolution. The structure reveals a hollow rhombohedral fold with a 2-fold symmetry...
March 22, 2018: Cell Research
https://www.readbyqxmd.com/read/29550823/rictor-deficiency-aggravates-hepatic-ischemia-reperfusion-injury-in-mice-by-suppressing-autophagy-and-regulating-mapk-signaling
#7
Dongwei Xu, Jianjun Zhu, Seogsong Jeong, Dawei Li, Xiangwei Hua, Lifeng Huang, Jianjun Zhang, Yi Luo, Qiang Xia
BACKGROUND/AIMS: The role of Rictor in hepatic ischemia/reperfusion (I/R) injury remains unknown. Here, we comprehensively examined the role of Rictor in hepatic I/R injury. METHODS: We studied the expression of Rictor during hepatic I/R injury. The regulatory effects of Rictor on inflammatory responses, cytokine and chemokine release, apoptotic and anti-apoptotic responses, and autophagy induction during hepatic I/R injury were identified via the shRNA-mediated knockdown of Rictor...
March 10, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29518209/a-germline-specific-role-for-the-mtorc2-component-rictor-in-maintaining-spermatogonial-differentiation-and-intercellular-adhesion-in-mouse-testis
#8
Shun Bai, Le Cheng, Yingwen Zhang, Chunsen Zhu, Zhiping Zhu, Ruping Zhu, C Yan Cheng, Lan Ye, Ke Zheng
STUDY QUESTION: What is the physiological role of Rictor in spermatogenic cells? SUMMARY ANSWER: Germline expression of Rictor regulates spermatogonial differentiation and has an essential role in coordinating germ cells and Sertoli cells in maintaining intact cell-cell adhesion dynamics and cytoskeleton-based architecture in the seminiferous epithelium. WHAT IS KNOWN ALREADY: The mechanistic target of rapamycin (mTOR) resides in its functions as the catalytic subunits of the structurally and functionally distinct mTORC1 and mTORC2 complexes...
February 6, 2018: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29514084/innate-immune-signaling-in-drosophila-blocks-insulin-signaling-by-uncoupling-pi-3-4-5-p-3-production-and-akt-activation
#9
Stephen W Roth, Moshe D Bitterman, Morris J Birnbaum, Michelle L Bland
In obese adipose tissue, Toll-like receptor signaling in macrophages leads to insulin resistance in adipocytes. Similarly, Toll signaling in the Drosophila larval fat body blocks insulin-dependent growth and nutrient storage. We find that Toll acts cell autonomously to block growth but not PI(3,4,5)P3 production in fat body cells expressing constitutively active PI3K. Fat body Toll signaling blocks whole-animal growth in rictor mutants lacking TORC2 activity, but not in larvae lacking Pdk1. Phosphorylation of Akt on the Pdk1 site, Thr342, is significantly reduced by Toll signaling, and expression of mutant AktT342D rescues cell and animal growth, nutrient storage, and viability in animals with active Toll signaling...
March 6, 2018: Cell Reports
https://www.readbyqxmd.com/read/29499960/mir-185-inhibits-fibrogenic-activation-of-hepatic-stellate-cells-and-prevents-liver-fibrosis
#10
Li Zhou, Shunai Liu, Ming Han, Yanhua Ma, Shenghu Feng, Jing Zhao, Hongping Lu, Xiaoxue Yuan, Jun Cheng
Recent studies have shown the effect of microRNAs on HSC activation and transformation, which is essential for the pathogenesis of liver fibrosis. In our study, we explored the role of miR-185 in liver fibrosis. Plasma miR-185 was detected in hepatitis B virus-related liver fibrosis patients (S2/3, n = 10) by Illumina HiSeq sequencing, and healthy volunteers were selected (n = 8) as the control group. We found that the plasma miR-185 level in fibrosis patients was significantly downregulated. CCl4 -induced fibrosis tissues in mouse livers and TGF-β1-activated HSCs also presented downregulated miR-185 concomitant with an increased expression of RHEB and RICTOR...
March 2, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/29497165/mtorc2-in-the-dorsomedial-striatum-of-mice-contributes-to-alcohol-dependent-f-actin-polymerization-structural-modifications-and-consumption
#11
Sophie Laguesse, Nadege Morisot, Khanhky Phamluong, Samuel A Sakhai, Dorit Ron
Actin is highly enriched at dendritic spines, and actin remodeling plays an essential role in structural plasticity. The mammalian target of rapamycin complex 2 (mTORC2) is a regulator of actin polymerization. Here, we report that alcohol consumption increases F-actin content in the dorsomedial striatum (DMS) of mice, thereby altering dendritic spine morphology in a mechanism that requires mTORC2. Specifically, we found that excessive alcohol consumption increases mTORC2 activity in the DMS, and that knockdown of Rictor, an essential component of mTORC2 signaling, reduces actin polymerization, and attenuates the alcohol-dependent alterations in spine head size and the number of mushroom spines...
June 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29487597/loss-of-rictor-in-monocyte-macrophages-suppresses-their-proliferation-and-viability-reducing-atherosclerosis-in-ldlr-null-mice
#12
Vladimir R Babaev, Jiansheng Huang, Lei Ding, Youmin Zhang, James M May, MacRae F Linton
Background: Rictor is an essential component of mammalian target of rapamycin (mTOR) complex 2 (mTORC2), a conserved serine/threonine kinase that may play a role in cell proliferation, survival and innate or adaptive immune responses. Genetic loss of Rictor inactivates mTORC2, which directly activates Akt S473 phosphorylation and promotes pro-survival cell signaling and proliferation. Methods and results: To study the role of mTORC2 signaling in monocytes and macrophages, we generated mice with myeloid lineage-specific Rictor deletion (M Rictor -/- )...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29475988/hla-class-ii-triggered-signaling-cascades-cause-endothelial-cell-proliferation-and-migration-relevance-to-antibody-mediated-transplant-rejection
#13
Yi-Ping Jin, Nicole M Valenzuela, Xiaohai Zhang, Enrique Rozengurt, Elaine F Reed
Transplant recipients developing donor-specific HLA class II (HLA-II) Abs are at higher risk for Ab-mediated rejection (AMR) and transplant vasculopathy. To understand how HLA-II Abs cause AMR and transplant vasculopathy, we determined the signaling events triggered in vascular endothelial cells (EC) following Ab ligation of HLA-II molecules. HLA-II expression in EC was induced by adenoviral vector expression of CIITA or by pretreatment with TNF-α/IFN-γ. Ab ligation of class II stimulated EC proliferation and migration...
April 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29460266/increased-levels-of-rictor-prevent-mutant-huntingtin-induced-neuronal-degeneration
#14
Jordi Creus-Muncunill, Laura Rué, Rafael Alcalá-Vida, Raquel Badillos-Rodríguez, Joan Romaní-Aumedes, Sonia Marco, Jordi Alberch, Isabel Perez-Otaño, Cristina Malagelada, Esther Pérez-Navarro
Rictor associates with mTOR to form the mTORC2 complex, which activity regulates neuronal function and survival. Neurodegenerative diseases are characterized by the presence of neuronal dysfunction and cell death in specific brain regions such as for example Huntington's disease (HD), which is characterized by the loss of striatal projection neurons leading to motor dysfunction. Although HD is caused by the expression of mutant huntingtin, cell death occurs gradually suggesting that neurons have the capability to activate compensatory mechanisms to deal with neuronal dysfunction and later cell death...
February 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29455662/the-role-of-rictor-downstream-of-receptor-tyrosine-kinase-in-cancers
#15
REVIEW
Ahlem Jebali, Nicolas Dumaz
The importance of the network defined by phosphatidylinositol-3-kinase (PI3K), AKT and mammalian target of rapamycin (mTOR) downstream of Receptor Tyrosine Kinase (RTK) has been known for many years but the central role of RICTOR (rapamycin-insensitive companion of mTOR) in this pathway is only starting to emerge. RICTOR is critical for mTORC2 (the mammalian target of rapamycin complex 2) kinase activity and as such plays a key role downstream of RTK. Alterations of RICTOR have been identified in a number of cancer cell types and its involvement in tumorigenesis has begun to be unraveled recently...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29432734/the-anti-osteosarcoma-cell-activity-by-a-mtorc1-2-dual-inhibitor-res-529
#16
Xujun Hu, Zirui Wang, Meikai Chen, Xuerong Chen, Wenqing Liang
mTOR over-activation is important for human osteosarcoma (OS) tumorigenesis and progression. RES-529 is a mTORC1/2 dual inhibitor. Here, our results show that RES-529 inhibited viability, cell cycle progression and proliferation of the established (U2OS line) and primary human OS cells. RES-529 induced apoptosis activation in OS cells. It was yet non-cytotoxic to OB-6 osteoblastic cells and the primary human osteoblasts. RES-529 disrupted assembling of mTORC1 (mTOR-Raptor association) and mTORC2 (mTOR-Rictor-mLST8 association) in human OS cells, blocking mTORC1/2 activation...
March 4, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29416920/everolimus-following-5-aza-2-deoxycytidine-is-a-promising-therapy-in-paclitaxel-resistant-clear-cell-carcinoma-of-the-ovary
#17
Chih-Ming Ho, Fa-Kung Lee, Shih-Hung Huang, Wen-Fang Cheng
Our previous study showed that 5-aza-2-deoxycytidine (5-aza-dC) could inhibit tumor growth by enhancing the susceptibility of ovarian clear cell carcinoma (OCCC) to paclitaxel through decreasing AKT/mTOR expressions. The objective of the study is to evaluate the antitumor efficacy of everolimus (RAD001) and 5-aza-2-deoxycytidine (5-aza-dC) by targeting AKT/mTOR and EZH2 in OCCC. Paclitaxel-sensitive and resistant OCCC cell lines were established. In vitro proliferative and apoptotic assays and flow cytometry were performed...
2018: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29415022/rictor-torc2-mediates-gut-to-brain-signaling-in-the-regulation-of-phenotypic-plasticity-in-c-elegans
#18
Michael P O'Donnell, Pin-Hao Chao, Jan E Kammenga, Piali Sengupta
Animals integrate external cues with information about internal conditions such as metabolic state to execute the appropriate behavioral and developmental decisions. Information about food quality and quantity is assessed by the intestine and transmitted to modulate neuronal functions via mechanisms that are not fully understood. The conserved Target of Rapamycin complex 2 (TORC2) controls multiple processes in response to cellular stressors and growth factors. Here we show that TORC2 coordinates larval development and adult behaviors in response to environmental cues and feeding state in the bacterivorous nematode C...
February 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29378959/effects-of-rapamycin-on-growth-hormone-receptor-knockout-mice
#19
Yimin Fang, Cristal M Hill, Justin Darcy, Adriana Reyes-Ordoñez, Edwin Arauz, Samuel McFadden, Chi Zhang, Jared Osland, John Gao, Tian Zhang, Stuart J Frank, Martin A Javors, Rong Yuan, John J Kopchick, Liou Y Sun, Jie Chen, Andrzej Bartke
It is well documented that inhibition of mTORC1 (defined by Raptor), a complex of mechanistic target of rapamycin (mTOR), extends life span, but less is known about the mechanisms by which mTORC2 (defined by Rictor) impacts longevity. Here, rapamycin (an inhibitor of mTOR) was used in GHR-KO (growth hormone receptor knockout) mice, which have suppressed mTORC1 and up-regulated mTORC2 signaling, to determine the effect of concurrently decreased mTORC1 and mTORC2 signaling on life span. We found that rapamycin extended life span in control normal (N) mice, whereas it had the opposite effect in GHR-KO mice...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29358172/selective-mtorc2-inhibitor-therapeutically-blocks-breast-cancer-cell-growth-and-survival
#20
Thomas A Werfel, Shan Wang, Meredith A Jackson, Taylor E Kavanaugh, Meghan Morrison Joly, Linus H Lee, Donna J Hicks, Violeta Sanchez, Paula Gonzalez Ericsson, Kameron V Kilchrist, Somtochukwu C Dimobi, Samantha M Sarett, Dana M Brantley-Sieders, Rebecca S Cook, Craig L Duvall
Small-molecule inhibitors of the mTORC2 kinase (torkinibs) have shown efficacy in early clinical trials. However, the torkinibs under study also inhibit the other mTOR-containing complex mTORC1. While mTORC1/mTORC2 combined inhibition may be beneficial in cancer cells, recent reports describe compensatory cell survival upon mTORC1 inhibition due to loss of negative feedback on PI3K, increased autophagy, and increased macropinocytosis. Genetic models suggest that selective mTORC2 inhibition would be effective in breast cancers, but the lack of selective small-molecule inhibitors of mTORC2 have precluded testing of this hypothesis to date...
April 1, 2018: Cancer Research
keyword
keyword
56904
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"