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Rac1 RhoA cancer

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https://www.readbyqxmd.com/read/29684861/inhibition-of-gastric-cancer-by-local-anesthetic-bupivacaine-through-multiple-mechanisms-independent-of-sodium-channel-blockade
#1
Jiapeng Dan, Xiaodan Gong, Dezhan Li, Guanhua Zhu, Lishen Wang, Fang Li
BACKGROUND: Retrospective studies of patients undergoing cancer surgery suggest the use of local anesthesia may decrease tumor recurrence and improve survival. The mechanisms on the benefits of local anesthesia on cancer recurrence are complex and remain to be elucidated. METHODS: This study investigated the effects of bupivacaine on various cellular activities of gastric cancer using proliferation, migration, apoptosis assay. The underlying mechanism was analyzed focusing on mitochondrial functions and the activities of Rho family members...
April 20, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29683214/piezo1-functions-as-a-potential-oncogene-by-promoting-cell-proliferation-and-migration-in-gastric-carcinogenesis
#2
Jinglin Zhang, Yuhang Zhou, Tingting Huang, Feng Wu, Liping Liu, Johnny S H Kwan, Alfred S L Cheng, Jun Yu, Ka Fai To, Wei Kang
Gastric cancer (GC) is one of the most common malignancies in Asian areas. PIEZO1 has been implied to regulate epithelial homeostasis to play an important role in physiological processes. It is also related to tumor initiation and progression. However, the role of PIEZO1 has not yet been explored in GC. The expression of PIEZO1 in GC cell lines and primary samples was determined by qRT-PCR and Western blot. The clinical correlation of PIEZO1 in GC was evaluated by immunohistochemistry on tissue microarray. The oncogenic role of PIEZO1 was demonstrated in gastric tumorigenesis through a series of functional assays, including cell proliferation, cell invasion and flow cytometry analysis...
April 23, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29615071/mature-and-progenitor-endothelial-cells-perform-angiogenesis-also-under-protease-inhibition-the-amoeboid-angiogenesis
#3
Anastasia Chillà, Francesca Margheri, Alessio Biagioni, Mario Del Rosso, Gabriella Fibbi, Anna Laurenzana
BACKGROUND: Controlling vascular growth is a challenging aim for the inhibition of tumor growth and metastasis. The amoeboid and mesenchymal types of invasiveness are two modes of migration interchangeable in cancer cells: the Rac-dependent mesenchymal migration requires the activity of proteases; the Rho-ROCK-dependent amoeboid motility is protease-independent and has never been described in endothelial cells. METHODS: A cocktail of physiologic inhibitors (Ph-C) of serine-proteases, metallo-proteases and cysteine-proteases, mimicking the physiological environment that cells encounter during their migration within the angiogenesis sites was used to induce amoeboid style migration of Endothelial colony forming cells (ECFCs) and mature endothelial cells (ECs)...
April 3, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29543440/multiplexed-real-time-nmr-gtpase-assay-for-simultaneous-monitoring-of-multiple-gef-activities-from-human-cancer-cells-and-organoids
#4
Teklab Gebregiworgis, Christopher Boyd Marshall, Tadateru Nishikawa, Nikolina Radulovich, María-José Sandi, Zhenhao Fang, Robert Rottapel, Ming-Sound Tsao, Mitsuhiko Ikura
Small GTPases (sGTPases) are critical switch-like regulators that mediate several important cellular functions and are often mutated in human cancers. They are activated by guanine nucleotide exchange factors (GEFs), which specifically catalyze the exchange of GTP for GDP. GEFs coordinate signaling networks in normal cells, and are frequently deregulated in cancers. sGTPase signaling pathways are complex and interconnected; however, most GEF assays do not reveal such complexity. In this communication, we describe the development of a unique real-time NMR-based multiplexed GEF assay that employs distinct isotopic labeling schemes for each sGTPase protein to enable simultaneous observation of six proteins of interest...
March 15, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29492190/targeting-ovarian-cancer-and-endothelium-with-an-allosteric-ptp4a3-phosphatase-inhibitor
#5
Kelley E McQueeney, Joseph M Salamoun, James C Burnett, Nektarios Barabutis, Paula Pekic, Sophie L Lewandowski, Danielle C Llaneza, Robert Cornelison, Yunpeng Bai, Zhong-Yin Zhang, John D Catravas, Charles N Landen, Peter Wipf, John S Lazo, Elizabeth R Sharlow
Overexpression of protein tyrosine phosphatase PTP4A oncoproteins is common in many human cancers and is associated with poor patient prognosis and survival. We observed elevated levels of PTP4A3 phosphatase in 79% of human ovarian tumor samples, with significant overexpression in tumor endothelium and pericytes. Furthermore, PTP4A phosphatases appear to regulate several key malignant processes, such as invasion, migration, and angiogenesis, suggesting a pivotal regulatory role in cancer and endothelial signaling pathways...
February 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29454618/natural-small-molecule-bigelovin-suppresses-orthotopic-colorectal-tumor-growth-and-inhibits-colorectal-cancer-metastasis-via-il6-stat3-pathway
#6
Mingyue Li, Grace Gar-Lee Yue, Li-Hua Song, Mao-Bo Huang, Julia Kin-Ming Lee, Stephen Kwok-Wing Tsui, Kwok-Pui Fung, Ning-Hua Tan, Clara Bik-San Lau
Bigelovin, a sesquiterpene lactone, has been demonstrated to induce apoptosis, inhibit inflammation and angiogenesis in vitro, but its potential anti-metastatic activity remains unclear. In the present study, two colon cancer mouse models, orthotopic tumor allografts and experimental metastatic models were utilized to investigate the progression and metastatic spread of colorectal cancer after bigelovin treatments. Results showed that bigelovin (intravenous injection; 0.3-3 mg/kg) significantly suppressed tumor growth and inhibited liver/lung metastasis with modulation of tumor microenvironment (e...
February 15, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29440144/spon2-promotes-m1-like-macrophage-recruitment-and-inhibits-hepatocellular-carcinoma-metastasis-by-distinct-integrin-rho-gtpase-hippo-pathways
#7
Yan-Li Zhang, Qing Li, Xiao-Mei Yang, Fang Fang, Jun Li, Ya-Hui Wang, Qin Yang, Lei Zhu, Hui-Zhen Nie, Xue-Li Zhang, Ming-Xuan Feng, Shu-Heng Jiang, Guang-Ang Tian, Li-Peng Hu, Ho-Young Lee, Su-Jae Lee, Qiang Xia, Zhi-Gang Zhang
Tumor-associated macrophages (TAM) represent key regulators of the complex interplay between cancer and the immune microenvironment. Matricellular protein SPON2 is essential for recruiting lymphocytes and initiating immune responses. Recent studies have shown that SPON2 has complicated roles in cell migration and tumor progression. Here we report that, in the tumor microenvironment of hepatocellular carcinoma (HCC), SPON2 not only promotes infiltration of M1-like macrophages but also inhibits tumor metastasis...
February 13, 2018: Cancer Research
https://www.readbyqxmd.com/read/29377591/carboxylated-graphene-oxide-promoted-axonal-guidance-growth-by-activating-netrin-1-dcc-signaling-in-rat-primary-cultured-cortical-neurons
#8
Meili Liu, Zhengtai Jia, Xiongfu Xiao, Zhifa Zhang, Ping Li, Gang Zhou, Yubo Fan
Nanomaterials of graphene and its derivatives have been widely applied in recent years, but whose impacts on the neuronal guidance growth are still not reported. In the present study, graphene oxide (GO) and Carboxylated graphene oxide (GO-COOH) were used to investigate the potential effects on axonal guidance growth in the primary cultured cortical neurons. In addition,we characterized the structure and chemical composition of synthesized graphene oxide (GO) and carboxylated graphene oxide (GO-COOH) using Fourier transform infrared (FT-IR) spectrophotometer and Scanning Electron Microscope (SEM) assays and Raman analysis...
January 29, 2018: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29312635/lrp6-promotes-invasion-and-metastasis-of-colorectal-cancer-through-cytoskeleton-dynamics
#9
Qian Yao, Yu An, Wei Hou, Ya-Nan Cao, Meng-Fei Yao, Ning-Ning Ma, Lin Hou, Hong Zhang, Hai-Jing Liu, Bo Zhang
Low density lipoprotein (LDL) receptor-related protein-6 (LRP6) is an important co-receptor of Wnt pathway, which plays a predominant role in development and progression of colorectal cancer. Recently, dysregulation of LRP6 has proved to be involved in the progression of cancers, but its biological role and clinical significance in colorectal cancer remain unclear. In present study, we revealed that phosphorylation of LRP6 was aberrantly upregulated in colorectal carcinoma correlating with TNM or Dukes staging and worse prognosis...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29279389/rsk2-drives-cell-motility-by-serine-phosphorylation-of-larg-and-activation-of-rho-gtpases
#10
Geng-Xian Shi, Won Seok Yang, Ling Jin, Michelle L Matter, Joe W Ramos
Directed migration is essential for cell motility in many processes, including development and cancer cell invasion. RSKs (p90 ribosomal S6 kinases) have emerged as central regulators of cell migration; however, the mechanisms mediating RSK-dependent motility remain incompletely understood. We have identified a unique signaling mechanism by which RSK2 promotes cell motility through leukemia-associated RhoGEF (LARG)-dependent Rho GTPase activation. RSK2 directly interacts with LARG and nucleotide-bound Rho isoforms, but not Rac1 or Cdc42...
January 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29236027/simvastatin-inhibits-cell-proliferation-and-migration-in-human-anaplastic-thyroid-cancer
#11
Mei-Chieh Chen, Yuan-Chin Tsai, Jen-Ho Tseng, Jr-Jiun Liou, Steve Horng, Heng-Ching Wen, Yu-Ching Fan, Wen-Bin Zhong, Sung-Po Hsu
Malignant human anaplastic thyroid cancer (ATC) is pertinacious to conventional therapies. The present study investigated the anti-cancer activity of simvastatin and its underlying regulatory mechanism in cultured ATC cells. Simvastatin (0-20 μM) concentration-dependently reduced cell viability and relative colony formation. Depletions of mevalonate (MEV) and geranylgeranyl pyrophosphate (GGpp) by simvastatin induced G1 arrest and increased apoptotic cell populations at the sub-G1 phase. Adding MEV and GGpp prevented the simvastatin-inhibited cell proliferation...
December 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29207169/daam1-activates-rhoa-to-regulate-wnt5a%C3%A2-induced-glioblastoma-cell-invasion
#12
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...
February 2018: 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
#13
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...
January 2018: 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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