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Rac1 RhoA cancer

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https://www.readbyqxmd.com/read/29207169/daam1-activates-rhoa-to-regulate-wnt5a%C3%A2-induced-glioblastoma-cell-invasion
#1
Guiyang Liu, Ting Yan, Xiaorong Li, Jianhui Sun, Bo Zhang, Hongjie Wang, Yichao Zhu
The signaling pathway of dishevelled-associated activator of morphogenesis 1 (Daam1) triggered by Wnt5a drives cell movement and migration during breast cancer metastasis. However, Wnt5a signaling in glioblastoma progression remains poorly defined. Wnt5a expression and activations of RhoA, Cdc42, and Rac1 were detected in human glioblastoma tissues by using ELISA assays and small G-protein activation assays, respectively. The cell invasion rate and Daam1 activation of glioblastoma U251 and T98MG cells were determined by cell invasion assays and pull-down assays, respectively...
December 1, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29050986/rac1-plays-a-role-in-cxcl12-but-not-ccl3-induced-chemotaxis-and-rac1-gef-inhibitor-nsc23766-has-off-target-effects-on-cxcr4
#2
Shirley C Mills, Lesley Howell, Andrew Beekman, Leanne Stokes, Anja Mueller
Cell migration towards a chemotactic stimulus relies on the re-arrangement of the cytoskeleton, which is triggered by activation of small G proteins RhoA, Rac1 and Cdc42, and leads to formation of lamellopodia and actin polymerisation amongst other effects. Here we show that Rac1 is important for CXCR4 induced chemotaxis but not for CCR1/CCR5 induced chemotaxis. For CXCL12-induced migration via CXCR4, breast cancer MCF-7 cells are reliant on Rac1, similarly to THP-1 monocytes and Jurkat T-cells. For CCL3-induced migration via CCR1 and/or CCR5, Rac1 signalling does not regulate cell migration in either suspension or adherent cells...
October 16, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29042792/low-dose-of-kaempferol-suppresses-the-migration-and-invasion-of-triple-negative-breast-cancer-cells-by-downregulating-the-activities-of-rhoa-and-rac1
#3
Shoushan Li, Ting Yan, Rong Deng, Xuesong Jiang, Huaping Xiong, Yuan Wang, Qiao Yu, Xiaohua Wang, Cheng Chen, Yichao Zhu
PURPOSE: Triple-negative breast cancer (TNBC) is an especially aggressive and hard-to-treat disease. Although the anticancer role of kaempferol has been reported in breast cancer, the effect of kaempferol on TNBC remains unclear. MATERIALS AND METHODS: This experiment investigated the migration-suppressive role of a low dose of kaempferol in TNBC cells. Wound-healing assays and cell invasion assays were used to confirm the migration and invasion of cells treated with kaempferol or transfected indicated constructs...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29039527/simvastatin-inhibits-the-expression-of-stemness%C3%A2-related-genes-and-the-metastatic-invasion-of-human-cancer-cells-via-destruction-of-the-cytoskeleton
#4
Rosarita Tatè, Enrica Zona, Rosanna De Cicco, Veronica Trotta, Maria Urciuoli, Alessandro Morelli, Salvatore Baiano, Rosa Carnuccio, Maria Pia Fuggetta, Franco Morelli
Statins are a class of drugs that inhibit the rate-limiting steps in the cholesterol biosynthesis pathway. They act by inhibiting 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate. Blocking of mevalonate synthesis leads to inhibition of the farnesylation and geranylgeranylation of several functional proteins, such as RhoA and other small guanosine triphosphate-binding proteins, that are important in maintaining the undifferentiated status of the cells...
October 13, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28915620/prpf-overexpression-induces-drug-resistance-through-actin-cytoskeleton-rearrangement-and-epithelial-mesenchymal-transition
#5
Salman Ul Islam, Adeeb Shehzad, Jong Kyung Sonn, Young Sup Lee
Pre-mRNA processing factor (PRPF) 4B kinase belongs to the CDK-like kinase family, and is involved in pre-mRNA splicing, and in signal transduction. In this study, we observed that PRPF overexpression decreased the intracellular levels of reactive oxygen species, and inhibited resveratrol-induced apoptosis by activating the cell survival signaling proteins NFκB, ERK, and c-MYC in HCT116 human colon cancer cells. PRPF overexpression altered cellular morphology, and rearranged the actin cytoskeleton, by regulating the activity of Rho family proteins...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28911825/paving-the-rho-in-cancer-metastasis-rho-gtpases-and-beyond
#6
REVIEW
Sepp Jansen, Reinoud Gosens, Thomas Wieland, Martina Schmidt
Malignant carcinomas are often characterized by metastasis, the movement of carcinoma cells from a primary site to colonize distant organs. For metastasis to occur, carcinoma cells first must adopt a pro-migratory phenotype and move through the surrounding stroma towards a blood or lymphatic vessel. Currently, there are very limited possibilities to target these processes therapeutically. The family of Rho GTPases is an ubiquitously expressed division of GTP-binding proteins involved in the regulation of cytoskeletal dynamics and intracellular signaling...
September 11, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28841878/the-role-of-lutheran-basal-cell-adhesion-molecule-in-human-bladder-carcinogenesis
#7
Hong-Yi Chang, Hsin-Mei Chang, Tsung-Jung Wu, Chang-Yao Chaing, Tzong-Shin Tzai, Hong-Lin Cheng, Giri Raghavaraju, Nan-Haw Chow, Hsiao-Sheng Liu
BACKGROUND: Lutheran/basal cell adhesion molecule (Lu/BCAM) is a membrane bound glycoprotein. This study was performed to investigate the role and downstream signaling pathway of Lu/BCAM in human bladder tumorigenesis. METHODS: Five human bladder cancer (E6, RT4, TSGH8301, TCCSUP and J82), one stable mouse fibroblast cell line (NIH-Lu) expressing Lu/BCAM transgene and sixty human uroepithelial carcinoma specimens were analyzed by real-time PCR, immunohistochemistry (IHC), immunofluorescence (IFA) staining, Western blotting and promoter luciferase assay for Lu/BCAM, respectively...
August 26, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28811522/the-lichen-secondary-metabolite-atranorin-suppresses-lung-cancer-cell-motility-and-tumorigenesis
#8
Rui Zhou, Yi Yang, So-Yeon Park, Thanh Thi Nguyen, Young-Woo Seo, Kyung Hwa Lee, Jae Hyuk Lee, Kyung Keun Kim, Jae-Seoun Hur, Hangun Kim
Lichens are symbiotic organisms that produce various secondary metabolites. Here, different lichen extracts were examined to identify secondary metabolites with anti-migratory activity against human lung cancer cells. Everniastrum vexans had the most potent inhibitory activity, and atranorin was identified as an active subcomponent of this extract. Atranorin suppressed β-catenin-mediated TOPFLASH activity by inhibiting the nuclear import of β-catenin and downregulating β-catenin/LEF and c-jun/AP-1 downstream target genes such as CD44, cyclin-D1 and c-myc...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28679472/nkcc1-regulates-migration-ability-of-glioblastoma-cells-by-modulation-of-actin-dynamics-and-interacting-with-cofilin
#9
Paula Schiapparelli, Hugo Guerrero-Cazares, Roxana Magaña-Maldonado, Susan M Hamilla, Sara Ganaha, Eric Goulin Lippi Fernandes, Chuan-Hsiang Huang, Helim Aranda-Espinoza, Peter Devreotes, Alfredo Quinones-Hinojosa
Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. The mechanisms that confer GBM cells their invasive behavior are poorly understood. The electroneutral Na(+)-K(+)-2Cl(-) co-transporter 1 (NKCC1) is an important cell volume regulator that participates in cell migration. We have shown that inhibition of NKCC1 in GBM cells leads to decreased cell migration, in vitro and in vivo. We now report on the role of NKCC1 on cytoskeletal dynamics. We show that GBM cells display a significant decrease in F-actin content upon NKCC1 knockdown (NKCC1-KD)...
July 2017: EBioMedicine
https://www.readbyqxmd.com/read/28657426/oncogenic-ect2-signaling-regulates-rrna-synthesis-in-nsclc
#10
Verline Justilien, Kayla C Lewis, Nicole R Murray, Alan P Fields
The Rho GTPase family members Rac1, Cdc42 and RhoA play key contributory roles in the transformed phenotype of human cancers. Epithelial Cell Transforming Sequence 2 (Ect2), a guanine nucleotide exchange factor (GEF) for these Rho GTPases, has also been implicated in a variety of human cancers. We have shown that Ect2 is frequently overexpressed in both major forms of non-small cell lung cancer (NSCLC), lung adenocarcinoma (LADC) and lung squamous cell carcinoma (LSCC), which together make up approximately 70% of all lung cancer diagnoses...
June 28, 2017: Small GTPases
https://www.readbyqxmd.com/read/28636424/fluid-shear-stress-regulates-hepg2-cell-migration-though-time-dependent-integrin-signaling-cascade
#11
Hongchi Yu, Yang Shen, Jingsi Jin, Yingying Zhang, Tang Feng, Xiaoheng Liu
Hepatocellular carcinoma (HCC) is a subtype of malignant liver cancer with poor prognosis and limited treatment options. It is noteworthy that mechanical forces in tumor microenvironment play a pivotal role in mediating the behaviors and functions of tumor cells. As an instrumental type of mechanical forces in vivo, fluid shear stress (FSS) has been reported having potent physiologic and pathologic effects on cancer progression. However, the time-dependent mechanochemical transduction in HCC induced by FSS remains unclear...
June 21, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28574815/prpf-overexpression-induces-drug-resistance-through-actin-cytoskeleton-rearrangement-and-epithelial-mesenchymal-transition
#12
Salman Ul Islam, Adeeb Shehzad, Jong Kyung Sonn, Young Sup Lee
Pre-mRNA processing factor (PRPF) 4B kinase belongs to the CDK-like kinase family, and is involved in pre-mRNA splicing, and in signal transduction. In this study, we observed that PRPF overexpression decreased the intracellular levels of reactive oxygen species, and inhibited resveratrol-induced apoptosis by activating the cell survival signaling proteins NFκB, ERK, and c-MYC in HCT116 human colon cancer cells. PRPF overexpression altered cellular morphology, and rearranged the actin cytoskeleton, by regulating the activity of Rho family proteins...
May 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28562340/cell-type-dependent-hif1-%C3%AE-mediated-effects-of-hypoxia-on-proliferation-migration-and-metastatic-potential-of-human-tumor-cells
#13
Enikő Tátrai, Alexandra Bartal, Alexandra Gacs, Sándor Paku, István Kenessey, Tamás Garay, Balázs Hegedűs, Eszter Molnár, Mihály T Cserepes, Zita Hegedűs, Nóra Kucsma, Gergely Szakács, József Tóvári
Tumor hypoxia promotes neoangiogenesis and contributes to the radio- and chemotherapy resistant and aggressive phenotype of cancer cells. However, the migratory response of tumor cells and the role of small GTPases regulating the organization of cytoskeleton under hypoxic conditions have yet to be established. Accordingly, we measured the proliferation, migration, RhoA activation, the mRNA and protein levels of hypoxia inducible factor-1alpha (HIF-1α) and three small G-proteins, Rac1, cdc42 and RhoA in a panel of five human tumor cell lines under normoxic and hypoxic conditions...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28549415/role-of-peptidylarginine-deiminase-2-pad2-in-mammary-carcinoma-cell-migration
#14
Sachi Horibata, Katherine E Rogers, David Sadegh, Lynne J Anguish, John L McElwee, Pragya Shah, Paul R Thompson, Scott A Coonrod
BACKGROUND: Penetration of the mammary gland basement membrane by cancer cells is a crucial first step in tumor invasion. Using a mouse model of ductal carcinoma in situ, we previously found that inhibition of peptidylarginine deiminase 2 (PAD2, aka PADI2) activity appears to maintain basement membrane integrity in xenograft tumors. The goal of this investigation was to gain insight into the mechanisms by which PAD2 mediates this process. METHODS: For our study, we modulated PAD2 activity in mammary ductal carcinoma cells by lentiviral shRNA-mediated depletion, lentiviral-mediated PAD2 overexpression, or PAD inhibition and explored the effects of these treatments on changes in cell migration and cell morphology...
May 26, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28423648/polyisoprenylated-cysteinyl-amide-inhibitors-disrupt-actin-cytoskeleton-organization-induce-cell-rounding-and-block-migration-of-non-small-cell-lung-cancer
#15
Elizabeth Ntantie, Jerrine Fletcher, Felix Amissah, Olufisayo O Salako, Augustine T Nkembo, Rosemary A Poku, Francis O Ikpatt, Nazarius S Lamango
The malignant potential of Non-Small Cell Lung Cancer (NSCLC) is dependent on cellular processes that promote metastasis. F-actin organization is central to cell migration, invasion, adhesion and angiogenesis, processes involved in metastasis. F-actin remodeling is enhanced by the overexpression and/or hyper-activation of some members of the Rho family of small GTPases. Therefore, agents that mitigate hyperactive Rho proteins may be relevant for controlling metastasis. We previously reported the role of polyisoprenylated cysteinyl amide inhibitors (PCAIs) as potential inhibitors of cancers with hyperactive small GTPases...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410221/discovery-and-characterization-of-small-molecule-rac1-inhibitors
#16
Jamie L Arnst, Ashley L Hein, Margaret A Taylor, Nick Y Palermo, Jacob I Contreras, Yogesh A Sonawane, Andrew O Wahl, Michel M Ouellette, Amarnath Natarajan, Ying Yan
Aberrant activation of Rho GTPase Rac1 has been observed in various tumor types, including pancreatic cancer. Rac1 activates multiple signaling pathways that lead to uncontrolled proliferation, invasion and metastasis. Thus, inhibition of Rac1 activity is a viable therapeutic strategy for proliferative disorders such as cancer. Here we identified small molecule inhibitors that target the nucleotide-binding site of Rac1 through in silico screening. Follow up in vitro studies demonstrated that two compounds blocked active Rac1 from binding to its effector PAK1...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28371345/the-prostate-metastasis-suppressor-gene-ndrg1-differentially-regulates-cell-motility-and-invasion
#17
Anup Sharma, Janet Mendonca, James Ying, Hea-Soo Kim, James E Verdone, Jelani C Zarif, Michael Carducci, Hans Hammers, Kenneth J Pienta, Sushant Kachhap
Experimental and clinical evidence suggests that N-myc downregulated gene 1 (NDRG1) functions as a suppressor of prostate cancer metastasis. Elucidating pathways that drive survival and invasiveness of NDRG1-deficient prostate cancer cells can help in designing therapeutics to target metastatic prostate cancer cells. However, the molecular mechanisms that lead NDRG1-deficient prostate cancer cells to increased invasiveness remain largely unknown. In this study, we demonstrate that NDRG1-deficient prostate tumors have decreased integrin expression and reduced cell adhesion and motility...
June 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28344327/mevalonate-cascade-inhibition-by-simvastatin-induces-the-intrinsic-apoptosis-pathway-via-depletion-of-isoprenoids-in-tumor-cells
#18
Javad Alizadeh, Amir A Zeki, Nima Mirzaei, Sandipan Tewary, Adel Rezaei Moghadam, Aleksandra Glogowska, Pandian Nagakannan, Eftekhar Eftekharpour, Emilia Wiechec, Joseph W Gordon, Fred Y Xu, Jared T Field, Ken Y Yoneda, Nicholas J Kenyon, Mohammad Hashemi, Grant M Hatch, Sabine Hombach-Klonisch, Thomas Klonisch, Saeid Ghavami
The mevalonate (MEV) cascade is responsible for cholesterol biosynthesis and the formation of the intermediate metabolites geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP) used in the prenylation of proteins. Here we show that the MEV cascade inhibitor simvastatin induced significant cell death in a wide range of human tumor cell lines, including glioblastoma, astrocytoma, neuroblastoma, lung adenocarcinoma, and breast cancer. Simvastatin induced apoptotic cell death via the intrinsic apoptotic pathway...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28235899/dual-targeting-of-mesenchymal-and-amoeboid-motility-hinders-metastatic-behavior
#19
Brandon C Jones, Laura C Kelley, Yuriy V Loskutov, Kristina M Marinak, Varvara K Kozyreva, Matthew B Smolkin, Elena N Pugacheva
Commonly upregulated in human cancers, the scaffolding protein NEDD9/HEF1 is a known regulator of mesenchymal migration and cancer cell plasticity. However, the functional role of NEDD9 as a regulator of different migration/invasion modes in the context of breast cancer metastasis is currently unknown. Here, it is reported that NEDD9 is necessary for both mesenchymal and amoeboid individual cell migration/invasion in triple-negative breast cancer (TNBC). NEDD9 deficiency results in acquisition of the amoeboid morphology, but severely limits all types of cell motility...
June 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28214467/paxillin-a-crossroad-in-pathological-cell-migration
#20
REVIEW
Ana María López-Colomé, Irene Lee-Rivera, Regina Benavides-Hidalgo, Edith López
Paxilllin is a multifunctional and multidomain focal adhesion adapter protein which serves an important scaffolding role at focal adhesions by recruiting structural and signaling molecules involved in cell movement and migration, when phosphorylated on specific Tyr and Ser residues. Upon integrin engagement with extracellular matrix, paxillin is phosphorylated at Tyr31, Tyr118, Ser188, and Ser190, activating numerous signaling cascades which promote cell migration, indicating that the regulation of adhesion dynamics is under the control of a complex display of signaling mechanisms...
February 18, 2017: Journal of Hematology & Oncology
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