keyword
MENU ▼
Read by QxMD icon Read
search

Rac1 RhoA cancer

keyword
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
#1
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
#2
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
#3
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...
April 2, 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
#4
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
#5
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...
February 24, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28214467/paxillin-a-crossroad-in-pathological-cell-migration
#6
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
https://www.readbyqxmd.com/read/28196303/long-noncoding-rna-schlah-suppresses-metastasis-of-hepatocellular-carcinoma-through-interacting-with-fused-in-sarcoma
#7
Zhouhong Ge, Zhuoan Cheng, Xinrong Yang, Xisong Huo, Ning Wang, Hui Wang, Cun Wang, Dishui Gu, Fangyu Zhao, Ming Yao, Jia Fan, Wenxin Qin
Emerging evidence has indicated that deregulation of long non-coding RNAs (lncRNAs) can contribute to the progression and metastasis of human cancer, including hepatocellular carcinoma (HCC). However, the roles of most lncRNAs in HCC remain largely unknown. Here we found a long noncoding RNA termed SchLAH (seven chromosome locus associated with HCC; also called BC035072) was generally downregulated in HCC. Low expression of SchLAH was significantly correlated with shorter overall survival of HCC patients. In vitro and in vivo assays indicated that overexpression of SchLAH inhibited the migration and lung metastasis of HCC cells...
April 2017: Cancer Science
https://www.readbyqxmd.com/read/28109909/erk2-zeb1-mir-101-1-axis-contributes-to-epithelial-mesenchymal-transition-and-cell-migration-in-cancer
#8
Kailash Chandra Mangalhara, Siddharth Manvati, Sunil Kumar Saini, Kalaiarasan Ponnusamy, Gaurav Agarwal, Suresh K Abraham, Rameshwar N K Bamezai
Regulation of metastasis continues to remain enigmatic despite our improved understanding of cancer. Identification of microRNAs associated with metastasis in the recent past has provided a new hope. Here, we show how microRNA-101 (miR-101) regulates two independent processes of cellular metastasis by targeting pro-metastatic upstream regulatory transcription factors, ZEB1 and ZEB2, and downstream effector-actin modulators, RHOA and RAC1, providing a single target for therapeutic intervention. Further, we depict how down-regulation of miR-101 by extracellular signal-regulated kinase-2 (ERK2) is vital for MAP kinase pathway induced cellular migration and mesenchymal transition...
January 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28068967/enterolactone-alters-fak-src-signaling-and-suppresses-migration-and-invasion-of-lung-cancer-cell-lines
#9
Shireen Chikara, Kaitlin Lindsey, Pawel Borowicz, Melpo Christofidou-Solomidou, Katie M Reindl
BACKGROUND: Systemic toxicity of chemotherapeutic agents and the challenges associated with targeting metastatic tumors are limiting factors for current lung cancer therapeutic approaches. To address these issues, plant-derived bioactive components have been investigated for their anti-cancer properties because many of these agents are non-toxic to healthy tissues. Enterolactone (EL) is a flaxseed-derived mammalian lignan that has demonstrated anti-migratory properties for various cancers, but EL has not been investigated in the context of lung cancer, and its anticancer mechanisms are ill-defined...
January 9, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27991930/rho-gtpases-anti-or-pro-neoplastic-targets
#10
REVIEW
I Zandvakili, Y Lin, J C Morris, Y Zheng
Rho GTPases are critical signal transducers of multiple pathways. They have been proposed to be useful anti-neoplastic targets for over two decades, especially in Ras-driven cancers. Until recently, however, few in vivo studies had been carried out to test this premise. Several recent mouse model studies have verified that Rac1, RhoA, and some of their effector proteins such as PAK and ROCK, are likely anti-cancer targets for treating K-Ras-driven tumours. Other seemingly contradictory studies have suggested that at least in certain instances inhibition of individual Rho GTPases may paradoxically result in pro-neoplastic effects...
December 19, 2016: Oncogene
https://www.readbyqxmd.com/read/27986811/ephb3-stimulates-cell-migration-and-metastasis-in-a-kinase-dependent-manner-through-vav2-rho-gtpase-axis-in-papillary-thyroid-cancer
#11
Jing-Jing Li, Zhi-Jian Sun, Yan-Mei Yuan, Fen-Fen Yin, Yao-Gang Bian, Ling-Yun Long, Xue-Li Zhang, Dong Xie
Eph receptors, the largest subfamily of transmembrane tyrosine kinase receptors, have been increasingly implicated in various physiologic and pathologic processes, and the roles of the Eph family members during tumorigenesis have recently attracted growing attentions. In the present study, we explored the function of EphB3, one member of Eph family, in papillary thyroid cancer (PTC). We found that the expression of EphB3 was significantly elevated in PTC. Either overexpression of EphB3 or activation of EphB3 by EfnB1-Fc/EfnB2-Fc stimulated in vitro migration of PTC cells...
January 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27913679/modelling-gtpase-dynamics-to-understand-rhoa-driven-cancer-cell-invasion
#12
REVIEW
Joseph H R Hetmanski, Jean-Marc Schwartz, Patrick T Caswell
Metastasis, initially driven by cells migrating and invading through the local environment, leads to most cancer-associated deaths. Cells can use a variety of modes to move in vitro, all of which depend on Rho GTPases at some level. While traditionally it was thought that Rac1 activity drives protrusive lamellipodia at the leading edge of a polarised cell while RhoA drives rear retraction, more recent work in 3D microenvironments has revealed a much more complicated picture of GTPase dynamics. In particular, RhoA activity can dominate the leading edge polymerisation of actin to form filopodial actin-spike protrusions that drive more invasive cell migration...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27754741/arf6-and-its-zeb1-epb41l5-mesenchymal-axis-are-required-for-both-mesenchymal-and-amoeboid-type-invasion-of-cancer-cells
#13
Haruka Handa, Ari Hashimoto, Shigeru Hashimoto, Hisataka Sabe
Modes of cancer invasion interchange between the mesenchymal type and amoeboid type in response to the microenvironment, in which RhoA and Rac1 are selectively required to perform different modes of actin-cytoskeletal remodeling. Membrane remodeling is another integral part of invasion. Arf6 regulates the recycling of molecules at the cell periphery, and is often overexpressed in malignant cancers together with its effector AMAP1/ASAP1/DDEF1. This pathway promotes mesenchymal-type invasion when AMAP1 binds to EPB41L5, a mesenchymal-specific protein induced by ZEB1...
October 18, 2016: Small GTPases
https://www.readbyqxmd.com/read/27726098/downregulation-of-arhgdia-contributes-to-human-glioma-progression-through-activation-of-rho-gtpase-signaling-pathway
#14
Weiliang Lu, Xixi Wang, Jingjing Liu, Yu He, Ziwei Liang, Zijing Xia, Ying Cai, Liangxue Zhou, Hongxia Zhu, Shufang Liang
The protein ARHGDIA has been found to play distinct roles in cancer progression for several tumors. However, it remains elusive whether and how ARHGDIA plays functions in human glioma. In this study, we discovered that ARHGDIA is much downregulated in human glioma; meanwhile, its expression negatively correlates with glioma malignancy and positively relates to prognosis of glioma patients. It has independent predictive value of ARHGDIA expression level for overall survival of human glioma patients. Glioma patients with ARHGDIA-positive expression have a longer overall survival time than ARHGDIA-negative patients...
October 10, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27715394/orphan-g-protein-coupled-receptor-gprc5a-modulates-integrin-%C3%AE-1-mediated-epithelial-cell-adhesion
#15
Daria R Bulanova, Yevhen A Akimov, Anne Rokka, Teemu D Laajala, Tero Aittokallio, Petri Kouvonen, Teijo Pellinen, Sergey G Kuznetsov
G-Protein Coupled Receptor (GPCR), Class C, Group 5, Member A (GPRC5A) has been implicated in several malignancies. The underlying mechanisms, however, remain poorly understood. Using a panel of human cell lines, we demonstrate that CRISPR/Cas9-mediated knockout and RNAi-mediated depletion of GPRC5A impairs cell adhesion to integrin substrates: collagens I and IV, fibronectin, as well as to extracellular matrix proteins derived from the Engelbreth-Holm-Swarm (EHS) mouse sarcoma (Matrigel). Consistent with the phenotype, knock-out of GPRC5A correlated with a reduced integrin β1 (ITGB1) protein expression, impaired phosphorylation of the focal adhesion kinase (FAK), and lower activity of small GTPases RhoA and Rac1...
October 7, 2016: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/27715393/expression-of-kindlin-3-in-melanoma-cells-impedes-cell-migration-and-metastasis
#16
Chen Feng, Wei-Kiat Wee, Huizhi Chen, Li-Teng Ong, Jing Qu, Hui-Foon Tan, Suet-Mien Tan
Kindlins are a small family of 4.1-ezrin-radixin-moesin (FERM)-containing cytoplasmic proteins. Kindlin-3 is expressed in platelets, hematopoietic cells, and endothelial cells. Kindlin-3 promotes integrin activation, clustering and outside-in signaling. Aberrant expression of kindlin-3 was reported in melanoma and breast cancer. Intriguingly, kindlin-3 has been reported to either positively or negatively regulate cancer cell metastasis. In this study, we sought to clarify the expression of kindlin-3 in melanoma cells and its role in melanoma metastasis...
October 7, 2016: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/27697106/gpr78-promotes-lung-cancer-cell-migration-and-metastasis-by-activation-of-g%C3%AE-q-rho-gtpase-pathway
#17
Dan-Dan Dong, Hui Zhou, Gao Li
GPR78 is an orphan G-protein coupled receptor (GPCR) that is predominantly expressed in human brain tissues. Currently, the function of GPR78 is unknown. This study revealed that GPR78 was expressed in lung cancer cells and functioned as a novel regulator of lung cancer cell migration and metastasis. We found that knockdown of GPR78 in lung cancer cells suppressed cell migration. Moreover, GPR78 modulated the formation of actin stress fibers in A549 cells, in a RhoA- and Rac1-dependent manner. At the molecular level, GPR78 regulated cell motility through the activation of Gαq-RhoA/Rac1 pathway...
November 2016: BMB Reports
https://www.readbyqxmd.com/read/27628050/rho-gtpases-regulation-and-roles-in-cancer-cell-biology
#18
Raquel B Haga, Anne J Ridley
Rho GTPases are well known for their roles in regulating cell migration, and also contribute to a variety of other cellular responses. They are subdivided into 2 groups: typical and atypical. The typical Rho family members, including RhoA, Rac1 and Cdc42, cycle between an active GTP-bound and inactive GDP-bound conformation, and are regulated by GEFs, GAPs and GDIs, whereas atypical Rho family members have amino acid substitutions that alter their ability to interact with GTP/GDP and hence are regulated by different mechanisms...
October 2016: Small GTPases
https://www.readbyqxmd.com/read/27589842/cross-linked-hyaluronic-acid-gel-inhibits-metastasis-and-growth-of-gastric-and-hepatic-cancer-cells-in-vitro-and-in-vivo-studies
#19
Ting Lan, Ji Pang, Yan Wu, Miaolin Zhu, Xiaoyuan Yao, Min Wu, Hai Qian, Zhenyu Zhang, Jizong Gao, Yongchang Chen
Cross-linked hyaluronic acid gel (CHAG) has been used to prevent postoperative adhesion of abdominal tumorectomy. However, its effect on tumor cells is still unknown. This paper was designed to investigate the effect of CHAG on metastasis and growth of tumor cells. Migration and invasion assays, Western blotting, pull down assay, siRNA interference, and nude mice implantation tumor model were applied in this study. The results of in vitro experiments with gastric cancer cell line AGS and hepatic cancer cell line HepG2 showed that CHAG inhibited the migration and invasion activities, the MAPK and PI3K/Akt mediated signaling, the activation of small G proteins Rac1 and RhoA, and the expression of MMPs and PCNA initiated by EGF, through blocking the activation of EGFR...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27452906/prl-3-engages-the-focal-adhesion-pathway-in-triple-negative-breast-cancer-cells-to-alter-actin-structure-and-substrate-adhesion-properties-critical-for-cell-migration-and-invasion
#20
Hamid H Gari, Gregory D DeGala, Rahul Ray, M Scott Lucia, James R Lambert
Triple-negative breast cancers (TNBCs) are among the most aggressive cancers characterized by a high propensity to invade, metastasize and relapse. We previously reported that the TNBC-specific inhibitor, AMPI-109, significantly impairs the ability of TNBC cells to migrate and invade by reducing levels of the metastasis-promoting phosphatase, PRL-3. Here, we examined the mechanisms by which AMPI-109 and loss of PRL-3 impede cell migration and invasion. AMPI-109 treatment or knock down of PRL-3 expression were associated with deactivation of Src and ERK signaling and concomitant downregulation of RhoA and Rac1/2/3 GTPase protein levels...
October 1, 2016: Cancer Letters
keyword
keyword
54441
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"