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Ras protein

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https://www.readbyqxmd.com/read/28441755/role-of-rheb-in-regulating-differentiation-fate-of-mesenchymal-stem-cells-for-cartilage-and-bone-regeneration
#1
Sajjad Ashraf, In-Bo Han, Hansoo Park, Soo-Hong Lee
Advances in mesenchymal stem cells (MSCs) and cell replacement therapies are promising approaches to treat cartilage and bone defects since substantial differentiation capacities of MSCs match the demands of tissue regeneration. Our understanding of the dynamic process requiring indispensable differentiation of MSCs remains limited. Herein, we describe the role of RHEB (Ras homolog enriched in brain) regulating gene signature for differentiation of human adipose derived mesenchymal stem cells (ASCs) into chondrogenic, osteogenic, and adipogenic lineages...
April 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28439535/a-murine-preclinical-syngeneic-transplantation-model-for-breast-cancer-precision-medicine
#2
Lorenzo Federico, Zechen Chong, Dong Zhang, Daniel J McGrail, Wei Zhao, Kang Jin Jeong, Christopher P Vellano, Zhenlin Ju, Mihai Gagea, Shuying Liu, Shreya Mitra, Jennifer B Dennison, Philip L Lorenzi, Robert Cardnell, Lixia Diao, Jing Wang, Yiling Lu, Lauren A Byers, Charles M Perou, Shiaw-Yih Lin, Gordon B Mills
We previously demonstrated that altered activity of lysophosphatidic acid in murine mammary glands promotes tumorigenesis. We have now established and characterized a heterogeneous collection of mouse-derived syngeneic transplants (MDSTs) as preclinical platforms for the assessment of personalized pharmacological therapies. Detailed molecular and phenotypic analyses revealed that MDSTs are the most heterogeneous group of genetically engineered mouse models (GEMMs) of breast cancer yet observed. Response of MDSTs to trametinib, a mitogen-activated protein kinase (MAPK) kinase inhibitor, correlated with RAS/MAPK signaling activity, as expected from studies in xenografts and clinical trials providing validation of the utility of the model...
April 2017: Science Advances
https://www.readbyqxmd.com/read/28433697/rab22a-enhances-cd147-recycling-and-is-required-for-lung-cancer-cell-migration-and-invasion
#3
Yang Zhou, Bo Wu, Jiang-Hua Li, Gang Nan, Jian-Li Jiang, Zhi-Nan Chen
Rab22a is a member of the Ras-related small GTPase family, which plays a key role in regulating the recycling of cargo proteins entering cells through clathrin-independent endocytosis (CIE). Rab22a is overexpressed in different cancer types, including liver cancer, malignant melanoma, ovarian cancer and osteosarcoma. However, its oncogenic role remains unknown. In this study, we found that silencing of Rab22a suppressed the migration and invasion of lung cancer cells. Furthermore, Rab22a interacts with CD147, and knockdown of Rab22a blocks CD147 recycling and promotes CD147 degradation...
April 19, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28433077/development-and-clinical-utility-of-a-blood-based-test-service-for-the-rapid-identification-of-actionable-mutations-in-non-small-cell-lung-carcinoma
#4
Hestia Mellert, Trudi Foreman, Leisa Jackson, Dianna Maar, Scott Thurston, Kristina Koch, Amanda Weaver, Samantha Cooper, Nicholas Dupuis, Ubaradka G Sathyanarayana, Jakkie Greer, Westen Hahn, Dawne Shelton, Paula Stonemetz, Gary A Pestano
Nearly 80% of cancer patients do not have genetic mutation results available at initial oncology consultation; up to 25% of patients begin treatment before receiving their results. These factors hinder the ability to pursue optimal treatment strategies. This study validates a blood-based genome-testing service that provides accurate results within 72 hours. We focused on targetable variants in advanced non-small cell lung carcinoma-epidermal growth factor receptor gene (EGFR) variant L858R, exon 19 deletion (ΔE746-A750), and T790M; GTPase Kirsten ras gene (KRAS) variants G12C/D/V; and echinoderm microtubule associated protein like and 4 anaplastic lymphoma receptor tyrosine kinase fusion (EML4-ALK) transcripts 1/2/3...
May 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28431975/liposomal-curcumin-alters-chemosensitivity-of-breast-cancer-cells-to-adriamycin-via-regulating-microrna-expression
#5
Siying Zhou, Jian Li, Hanzi Xu, Sijie Zhang, Xiu Chen, Wei Chen, Sujin Yang, Shanliang Zhong, Jianhua Zhao, Jinhai Tang
BACKGROUND: Emerging evidence suggests that curcumin can overcome drug resistance to classical chemotherapies, but poor bioavailability and low absorption have limited its clinical use and the mechanisms remain unclear. Also, Adriamycin (Adr) is one of the most active cytotoxic agents in breast cancer; however, the high resistant rate of Adr leads to a poor prognosis. METHODS: We utilized encapsulation in liposomes as a strategy to improve the bioavailability of curcumin and demonstrated that liposomal curcumin altered chemosensitivity of Adr-resistant MCF-7 human breast cancer (MCF-7/Adr) by MTT assay...
April 18, 2017: Gene
https://www.readbyqxmd.com/read/28431272/specific-microrna-mrna-regulatory-network-of-colon-cancer-invasion-mediated-by-tissue-kallikrein-related-peptidase-6
#6
Earlphia Sells, Ritu Pandey, Hwudaurw Chen, Bethany A Skovan, Haiyan Cui, Natalia A Ignatenko
Metastatic colon cancer is a major cause of deaths among colorectal cancer (CRC) patients. Elevated expression of kallikrein 6 (KLK6), a member of a kallikrein subfamily of peptidase S1 family serine proteases, has been reported in CRC and is associated with low patient survival rates and poor disease prognosis. We knocked down KLK6 expression in HCT116 colon cancer cells to determine the significance of KLK6 expression for metastatic dissemination and to identify the KLK6-associated microRNAs (miRNAs) signaling networks in metastatic colon cancer...
April 18, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28428697/geraniol-inhibits-endometrial-carcinoma-via-downregulating-oncogenes-and-upregulating-tumour-suppressor-genes
#7
Sakkaravarthy Shanmugapriya, Perumal Subramanian, Sivamani Kanimozhi
Endometrial carcinoma is the fourth most abundant cancer worldwide in women. Female Wistar rats were segregated into five groups: group I-control, group II-MNNG (N-methyl-N'-nitro-N-nitrosoguanidine-150 mg/kg) administered through intravaginal detention of cotton absorbent, group III-geraniol (GOH) only, group IV-GOH-pretreated (7 days before the start of MNNG administration); and group V-Co-administration of geraniol with MNNG. In this study, reverse transcriptase- PCR of K-ras, MAPK, PI3K, Wnt/β-catenin genes, TGF-β and expressions of PCNA, PTEN, progesterone receptor and E-cadherin by Western blotting were performed from endometrial cancer tissue and control tissues...
June 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28426742/multiple-components-of-pka-and-tgf-%C3%AE-pathways-are-mutated-in-pseudomyxoma-peritonei
#8
Lilli Saarinen, Pirjo Nummela, Alexandra Thiel, Rainer Lehtonen, Petrus Järvinen, Heikki Järvinen, Lauri A Aaltonen, Anna Lepistö, Sampsa Hautaniemi, Ari Ristimäki
Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma mainly restricted to the peritoneal cavity and most commonly originating from the appendix. The genetic background of PMP is poorly understood and no targeted treatments are currently available for this fatal disease. While RAS signaling pathway is affected in most if not all PMP cases and over half of them also have a mutation in the GNAS gene, other genetic alterations and affected pathways are, to a large degree, poorly known. In this study, we sequenced whole coding genome of nine PMP tumors and paired normal tissues in order to identify additional, commonly mutated genes and signaling pathways affected in PMP...
2017: PloS One
https://www.readbyqxmd.com/read/28426288/post-translational-modifications-of-rab-gtpases
#9
Swapnil Rohidas Shinde, Subbareddy Maddika
Rab GTPases, the highly conserved members of Ras GTPase superfamily are central players in the vesicular trafficking. They are critically involved in intracellular trafficking pathway, beginning from formation of vesicles on donor membranes, defining trafficking specificity to facilitating vesicle docking on target membranes. Given the dynamic roles of Rabs during different stages of vesicular trafficking, mechanisms for their spatial and temporal regulation are crucial for normal cellular function. Regulation of Rab GTPase activity, localization and function has always been focused in and around the association of GDP dissociation inhibitor (GDI), Guanine nucleotide Exchange Factor (GEFs) and GTPase accelerating protein (GAP) to Rabs...
February 28, 2017: Small GTPases
https://www.readbyqxmd.com/read/28423706/identification-of-ras-suppressor-1-rsu-1-as-a-potential-breast-cancer-metastasis-biomarker-using-a-three-dimensional-in-vitro-approach
#10
Vasiliki Gkretsi, Andreas Stylianou, Maria Louca, Triantafyllos Stylianopoulos
Breast cancer (BC) is the most common malignant disease in women, with most patients dying from metastasis to distant organs, making discovery of novel metastasis biomarkers and therapeutic targets imperative. Extracellular matrix (ECM)-related adhesion proteins as well as tumor matrix stiffness are important determinants for metastasis. As traditional two-dimensional culture does not take into account ECM stiffness, we employed 3-dimensional collagen I gels of increasing concentration and stiffness to embed BC cells of different invasiveness (MCF-7, MDA-MB-231 and MDA-MB-231-LM2) or tumor spheroids...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423630/insufficient-hypothalamic-angiotensin-converting-enzyme-2-is-associated-with-hypertension-in-shr-rats
#11
Kun Wang, Yuanyuan Xu, Weiwei Yang, Yuanshu Zhang
Angiotensin-Converting Enzyme 2 (ACE2) is a key enzyme in the renin-angiotensin system (RAS), which is implicated in the pathogenesis of hypertension and other cardiovascular diseases. In this study we investigated the expression of ACE2 in the hypothalamus and pituitary tissues and its relationship to hypertension by comparing them in male WKY and SHR rats. We observed that the plasma levels of corticotrophin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and aldosterone (ALD) were all lower in SHR than WKY rats (P<0...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423577/the-cyclin-like-protein-spy1-regulates-the-er%C3%AE-and-erk1-2-pathways-promoting-tamoxifen-resistance
#12
Rosa-Maria Ferraiuolo, Janice Tubman, Indrajit Sinha, Caroline Hamm, Lisa Ann Porter
The Ras/Raf/MEK/ERK pathway conveys growth factor and mitogen signalling to control the phosphorylation of a plethora of substrates regulating proliferation, survival, and migration. The Ras signalling pathway is frequently associated with poor prognosis and drug resistance in various cancers including those of the blood, breast and prostate. Activation of the downstream effector ERK does not always occur via a linear cascade of events; complicating the targeting of this pathway therapeutically. This work describes a novel positive feedback loop where the cell cycle regulatory factor Spy1 (RINGO; gene SPDYA) activates ERK1/2 in a MEK-independent fashion...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418865/anti-helminthic-niclosamide-inhibits-ras-driven-oncogenic-transformation-via-activation-of-gsk-3
#13
Sung Yong Ahn, Ji Hye Yang, Nam Hee Kim, Kyungro Lee, Yong Hoon Cha, Jun Seop Yun, Hee Eun Kang, Yoonmi Lee, Jiwon Choi, Hyun Sil Kim, Jong In Yook
Despite the importance of Ras oncogenes as a therapeutic target in human cancer, their 'undruggable' tertiary structures limit the effectiveness of anti-Ras drugs. Canonical Wnt signaling contributes to Ras activity by glycogen synthase kinase 3 (GSK-3)-dependent phosphorylation at the C-terminus and subsequent degradation. In the accompanying report, we show that the anti-helminthic niclosamide directly binds to GSK-3 and inhibits Axin functions in colon cancer cells, with reversion of Snail-mediated epithelial-mesenchymal transition...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418088/rack1-forms-a-complex-with-fgfr1-and-pkm2-and-stimulates-the-growth-and-migration-of-squamous-lung-cancer-cells
#14
Chengzhi Zhou, Tao Chen, Zhanhong Xie, Yinyin Qin, Yangming Ou, Jiexia Zhang, Shiyue Li, Rongchang Chen, Nanshan Zhong
Phosphorylation of Pyruvate Kinase M2 (PKM2) on Tyr105 by fibroblast growth factor receptor 1 (FGFR1) has been shown to promote its nuclear localization as well as cell growth in lung cancer. Better understanding the regulation of this process would benefit the clinical treatment for lung cancer. Here, it has been found that the adaptor protein receptor for activated PKC kinase (RACK1) formed a complex with FGFR1 and PKM2, and activated the FGFR1/PKM2 signaling. Knocking down the expression of RACK1 impaired the phosphorylation on Tyr105 of PKM2 and inhibited the growth and migration of lung cancer cells, while over-expression of RACK1 in lung cancer cells led to the resistance to Erdafitinib...
April 18, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28416754/unique-synergistic-formulation-of-curcumin-epicatechin-gallate-and-resveratrol-tricurin-suppresses-hpv-e6-eliminates-hpv-cancer-cells-and-inhibits-tumor-progression
#15
Sumit Mukherjee, Priya Ranjan Debata, Rahman Hussaini, Kaushiki Chatterjee, Juliet N E Baidoo, Samay Sampat, Anita Szerszen, Joseph P Navarra, Jimmie Fata, Elena Severinova, Probal Banerjee, Mario R Castellanos
Curcumin (from curry) (C) is highly potent against cervical cancer cells (CCC), but poor bioavailability has limited its clinical use. Similar natural polyphenols resveratrol (from grapes) (R), and epicatechin gallate (from green tea) (E) also display activity against CCC. By treating CCC (HeLa) with C, E, or R, or combinations of these compounds, we computed combination indices and observed a strong synergism among C, E, and R at the unique molar ratio 4:1:12.5. This combination, named as TriCurin, rapidly down regulated HPV18 E6 and NF-kB expression while concomitantly inducing the tumor suppressor protein p53 in HeLa cells...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414306/targeting-prohibitins-with-chemical-ligands-inhibits-kras-mediated-lung-tumours
#16
H Yurugi, F Marini, C Weber, K David, Q Zhao, H Binder, L Désaubry, K Rajalingam
KRAS is one of the most frequently mutated oncogenes in human non-small cell lung cancers (NSCLCs). RAS proteins trigger multiple effector signalling pathways including the highly conserved RAF-MAPK pathway. CRAF, a direct RAS effector protein, is required for KRAS-mediated tumourigenesis. Thus, the molecular mechanisms driving the activation of CRAF are intensively studied. Prohibitin 1 (PHB1) is an evolutionarily conserved adaptor protein and interaction of CRAF with PHB1 at the plasma membrane is essential for CRAF activation...
April 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28414304/transforming-activity-and-therapeutic-targeting-of-c-terminal-binding-protein-2-in-apc-mutated-neoplasia
#17
E T Sumner, A T Chawla, A D Cororaton, J E Koblinski, R C Kovi, I M Love, B B Szomju, S Korwar, K C Ellis, S R Grossman
Overexpression of the transcriptional coregulators C-terminal binding proteins 1 and 2 (CtBP1 and 2) occurs in many human solid tumors and is associated with poor prognosis. CtBP modulates oncogenic gene expression programs and is an emerging drug target, but its oncogenic role is unclear. Consistent with this oncogenic potential, exogenous CtBP2 transformed primary mouse and human cells to anchorage independence similarly to mutant H-Ras. To investigate CtBP's contribution to in vivo tumorigenesis, Apc(min/+) mice, which succumb to massive intestinal polyposis, were bred to Ctbp2(+/-) mice...
April 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28413643/cytotoxic-and-antimigratory-effects-of-cratoxy-formosum-extract-against-hepg2-liver-cancer-cells
#18
Benjaporn Buranrat, Nootchanat Mairuae, Watchara Kanchanarach
The aim of the present study was to investigate the molecular mechanisms underlying Cratoxylum formosum (CF) Dyer-induced cancer cell death and antimigratory effects in HepG2 liver cancer cells. The cytotoxic, antiproliferative and antimigratory effects of CF leaf extract on human liver cancer HepG2 cell lines were evaluated using sulforhodamine B, colony formation, and wound healing assays. In addition, apoptosis induction mechanisms were investigated via reactive oxygen species (ROS) formation, caspase 3 activities, and mitochondrial membrane potential (ΔΨm) disruption...
April 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28413462/identification-of-mirna-biomarkers-of-pneumonia-using-rna-sequencing-and-bioinformatics-analysis
#19
Sai Huang, Cong Feng, Yong-Zhi Zhai, Xuan Zhou, Bei Li, Li-Li Wang, Wei Chen, Fa-Qin Lv, Tan-Shi Li
Pneumonia is a lower respiratory tract infection that causes dramatic mortality worldwide. The present study aimed to investigate the pathogenesis of pneumonia and identify microRNA (miRNA) biomarkers as candidates for targeted therapy. RNA from the peripheral blood plasma of participants with pneumonia (severe, n=9; non-severe, n=9) and controls (n=9) was isolated and paired-end sequencing was performed on an Illumina HiSeq4000 system. Following the processing of raw reads, the sequences were aligned against the Genome Reference Consortium human genome assembly 38 reference genome using Bowtie2 software...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28412885/antenatal-taurine-supplementation-in-fetal-rats-with-growth-restriction-improves-neural-stem-cell-proliferation-by-inhibiting-the-activities-of-rho-family-factors
#20
Yan Wang, Xiang-Wen Li, Jing Liu, Wei Fu
OBJECTIVE: To investigate whether antenatal taurine supplementation improves neural stem cell proliferation in rats with fetal growth restriction (FGR) through regulating the activity of Rho family factors. METHODS: FGR models were established via food restriction throughout pregnancy. Pregnant rats were randomly divided into the control group, the FGR group (given 40% of the normal daily feeding in the control group), and the Taurine group (FGR model treated with 300 mg/kg·d taurine from gestational day seven)...
April 16, 2017: Journal of Maternal-fetal & Neonatal Medicine
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