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Rac1 melanoma

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https://www.readbyqxmd.com/read/29222169/nanoscale-tuning-of-vcam-1-determines-vla-4-dependent-melanoma-cell-plasticity-on-rgd-motifs
#1
Katharina Amschler, Eugen Kossmann, Luise Erpenbeck, Sebastian Kruss, Tillmann Schill, Margarete Schön, Sigrid M C Möckel, Joachim P Spatz, Michael P Schön
The biophysical fine-tuning of cancer cell plasticity is crucial for tumor progression but remains largely enigmatic. Although Vascular Cell Adhesion Molecule-1 (VCAM-1/CD106) has been implicated in melanoma progression, here its presentation on endothelial cells was associated with diminished melanoma cell spreading. Using a specific nanoscale-modulation of VCAM-1 (tunable from 70 to 670 ligands/µm²) next to integrin ligands (RGD motifs) in a bifunctional system, reciprocal regulation of integrin α4 (ITGA4/VLA-4/CD49d)-dependent adhesion and spreading of melanoma cells was found...
December 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29095823/long-non-coding-rna-fth1p3-facilitates-uveal-melanoma-cell-growth-and-invasion-through-mir-224-5p
#2
Xiaoli Zheng, Hongwei Tang, Xiaofeng Zhao, Yamei Sun, Yanfang Jiang, Yonghua Liu
Growing evidences indicated that Long noncoding RNAs (lncRNAs) played important roles in tumor initiation and progression. However, the function and mechnism of lncRNA ferritin heavy chain 1 pseudogene 3 (FTH1P3) remain unknown in uveal melanoma. We showed that the expression level of FTH1P3 was upregulated in uveal melanoma cell lines and tissues. Elevated expression of FTH1P3 promoted uveal melanoma cell proliferation, cell cycle and migration. Moreover, we found that FTH1P3 was a direct target gene of miR-224-5p in uveal melanoma cell...
2017: PloS One
https://www.readbyqxmd.com/read/29059171/suppression-of-rac1-driven-malignant-melanoma-by-group-a-pak-inhibitors
#3
D Araiza-Olivera, Y Feng, G Semenova, T Y Prudnikova, J Rhodes, J Chernoff
Activating mutations in the RAC1 gene have recently been discovered as driver events in malignant melanoma. Expression of this gene is associated with melanocyte proliferation, and melanoma cells bearing this mutation are insensitive to BRAF inhibitors such as vemurafenib and dabrafenib, and also may evade immune surveillance due to enhanced expression of PD-L1. Activating mutations in RAC1 are of special interest, as small-molecule inhibitors for the RAC effector p21-activated kinase (PAK) are in late-stage clinical development and might impede oncogenic signaling from mutant RAC1...
October 23, 2017: Oncogene
https://www.readbyqxmd.com/read/28947953/the-inhibitory-effect-of-7-7%C3%A2-dimethoxyagastisflavone-on-the-metastasis-of-melanoma-cells-via-the-suppression-of-f-actin-polymerization
#4
Ching-Min Lin, Yu-Ling Lin, Shu-Yi Ho, Pin-Rong Chen, Yi-Hsuan Tsai, Chen-Han Chung, Chia-Hsiang Hwang, Nu-Man Tsai, Shey-Cherng Tzou, Chun-Yen Ke, Jung Chang, Yi-Lin Chan, Yu-Shan Wang, Kwan-Hwa Chi, Kuang-Wen Liao
7,7″-Dimethoxyagastisflavone (DMGF), a biflavonoid isolated from Taxus × media cv. Hicksii, induces apoptotic and autophagic cell death. However, whether DMGF suppresses tumor metastasis is unclear. The aim of this study was to investigate the anti-metastatic activities of DMGF on the metastatic processes of melanoma cells in vivo and in vitro. A transwell assay showed that DMGF could effectively attenuate the motility of B16F10 cells, and the results of real-time PCR revealed that DMGF also suppressed the expressions of matrix metalloproteinase-2 (MMP-2)...
September 1, 2017: Oncotarget
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/28803992/p-rex1-amplification-promotes-progression-of-cutaneous-melanoma-via-the-pak1-p38-mmp-2-pathway
#6
Jinhua Wang, Hajime Hirose, Guanhua Du, Kelly Chong, Eiji Kiyohara, Isaac P Witz, Dave S B Hoon
P-REX1 (PIP3-dependent Rac exchange factor-1) is a guanine nucleotide exchange factor that activates Rac by catalyzing exchange of GDP for GTP bound to Rac. Aberrant up-regulation of P-REX1 expression has a role in metastasis however, copy number (CN) and function of P-REX1 in cutaneous melanoma are unclear. To explore the role of P-REX1 in melanoma, SNP 6.0 and Exon 1.0 ST microarrays were assessed. There was a higher CN (2.82-fold change) of P-REX1 in melanoma cells than in melanocytes, and P-REX1 expression was significantly correlated with P-REX1 CN...
October 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28574815/prpf-overexpression-induces-drug-resistance-through-actin-cytoskeleton-rearrangement-and-epithelial-mesenchymal-transition
#7
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
#8
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/28416823/-identification-of-a-new-pro-invasion-factor-in-tumor-microenvironment-progress-in-function-and-mechanism-of-extracellular-atp
#9
W G Fang, X X Tian
Up to 90% of all cancer related morbidity and mortality can be attributed to metastasis. In recent years the study of tumor microenvironment, its cellular and molecular components, and how they can affect neoplastic progression toward metastasis, has become a hot focus in cancer research. Accumulated evidence shows that the formation of metastasis is a multi-step sequential process, in which, the tumor cells continuously interact with the host microenvironment. Host derived factors, i.e. growth factors/inhibitors, angiogenic factors, chemokines, etc...
April 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28277539/epidermal-rac1-regulates-the-dna-damage-response-and-protects-from-uv-light-induced-keratinocyte-apoptosis-and-skin-carcinogenesis
#10
Jayesh Deshmukh, Ruth Pofahl, Ingo Haase
Non-melanoma skin cancer (NMSC) is the most common type of cancer. Increased expression and activity of Rac1, a small Rho GTPase, has been shown previously in NMSC and other human cancers; suggesting that Rac1 may function as an oncogene in skin. DMBA/TPA skin carcinogenesis studies in mice have shown that Rac1 is required for chemically induced skin papilloma formation. However, UVB radiation by the sun, which causes DNA damage, is the most relevant cause for NMSC. A potential role of Rac1 in UV-light-induced skin carcinogenesis has not been investigated so far...
March 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28210865/the-impact-of-melanoma-genetics-on-treatment-response-and-resistance-in-clinical-and-experimental-studies
#11
M Kunz, M Hölzel
Recent attempts to characterize the melanoma mutational landscape using high-throughput sequencing technologies have identified new genes and pathways involved in the molecular pathogenesis of melanoma. Apart from mutated BRAF, NRAS, and KIT, a series of new recurrently mutated candidate genes with impact on signaling pathways have been identified such as NF1, PTEN, IDH1, RAC1, ARID2, and TP53. Under targeted treatment using BRAF and MEK1/2 inhibitors either alone or in combination, a majority of patients experience recurrences, which are due to different genetic mechanisms such as gene amplifications of BRAF or NRAS, MEK1/2 and PI3K mutations...
March 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28052407/p21-activated-kinase-1-regulates-resistance-to-braf-inhibition-in-human-cancer-cells
#12
Mahamat Babagana, Sydney Johnson, Hannah Slabodkin, Wiam Bshara, Carl Morrison, Eugene S Kandel
BRAF is a commonly mutated oncogene in various human malignancies and a target of a new class of anti-cancer agents, BRAF-inhibitors (BRAFi). The initial enthusiasm for these agents, based on the early successes in the management of metastatic melanoma, is now challenged by the mounting evidence of intrinsic BRAFi-insensitivity in many BRAF-mutated tumors, by the scarcity of complete responses, and by the inevitable emergence of drug resistance in initially responsive cases. These setbacks put an emphasis on discovering the means to increase the efficacy of BRAFi and to prevent or overcome BRAFi-resistance...
May 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27908735/unr-csde1-drives-a-post-transcriptional-program-to-promote-melanoma-invasion-and-metastasis
#13
COMMENT
Laurence Wurth, Panagiotis Papasaikas, David Olmeda, Nadine Bley, Guadalupe T Calvo, Santiago Guerrero, Daniela Cerezo-Wallis, Javier Martinez-Useros, María García-Fernández, Stefan Hüttelmaier, Maria S Soengas, Fátima Gebauer
RNA binding proteins (RBPs) modulate cancer progression through poorly understood mechanisms. Here we show that the RBP UNR/CSDE1 is overexpressed in melanoma tumors and promotes invasion and metastasis. iCLIP sequencing, RNA sequencing, and ribosome profiling combined with in silico studies unveiled sets of pro-metastatic factors coordinately regulated by UNR as part of RNA regulons. In addition to RNA steady-state levels, UNR was found to control many of its targets at the level of translation elongation/termination...
November 14, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27890785/genomic-characterization-of-dysplastic-nevi-unveils-implications-for-diagnosis-of%C3%A2-melanoma
#14
COMPARATIVE STUDY
Rachel D Melamed, Iraz T Aydin, Geena Susan Rajan, Robert Phelps, David N Silvers, Kevin J Emmett, Georg Brunner, Raul Rabadan, Julide Tok Celebi
A well-defined risk factor and precursor for cutaneous melanoma is the dysplastic nevus. These benign tumors represent clonal hyperproliferation of melanocytes that are in a senescent-like state, but with occasional malignant transformation events. To portray the mutational repertoire of dysplastic nevi in patients with the dysplastic nevus syndrome and to determine the discriminatory profiles of melanocytic nevi (including dysplastic nevi) from melanoma, we sequenced exomes of melanocytic nevi including dysplastic nevi (n = 19), followed by a targeted gene panel (785 genes) characterization of melanocytic nevi (n = 46) and primary melanomas (n = 42)...
April 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27846383/unrelenting-translation-unrestrains-melanoma-migration
#15
COMMENT
Ashani T Weeraratna, Myriam Gorospe
The cytoplasmic RNA-binding protein UNR influences key developmental processes by controlling mRNA turnover and translation initiation. In this issue of Cancer Cell, Wurth et al. report that UNR is highly expressed in melanoma and enhances invasion and metastasis at least partly by inducing translation elongation of VIM and RAC1 mRNAs.
November 14, 2016: Cancer Cell
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/27699663/impact-of-point-mutation-p29s-in-rac1-on-tumorigenesis
#17
Vidya Rajendran, Chandrasekhar Gopalakrishnan, Rituraj Purohit
A point mutation (P29S) in the RAS-related C3 botulinum toxin substrate 1 (RAC1) was considered to be a trigger for melanoma, a form of skin cancer with highest mortality rate. In this study, we have investigated the pathogenic role of P29S based on the conformational behavior of RAC1 protein toward guanosine triphosphate (GTP). Molecular interaction, molecular dynamics trajectory analysis (RMSD, RMSF, Rg, SASA, DSSP, and PCA), and shape analysis of binding pocket were performed to analyze the interaction energy and the dynamic behavior of native and mutant RAC1 at the atomic level...
November 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27575453/the-ig-vh-complementarity-determining-region-3-containing-rb9-peptide-inhibits-melanoma-cells-migration-and-invasion-by-interactions-with-hsp90-and-an-adhesion-g-protein-coupled-receptor
#18
Natalia Girola, Alisson L Matsuo, Carlos R Figueiredo, Mariana H Massaoka, Camyla F Farias, Denise C Arruda, Ricardo A Azevedo, Hugo P Monteiro, Pedro T Resende-Lara, Rodrigo L O R Cunha, Luciano Polonelli, Luiz R Travassos
The present work aims at investigating the mechanism of action of the Rb9 peptide, which contains the VHCDR 3 sequence of anti-sodium-dependent phosphate transport protein 2B (NaPi2B) monoclonal antibody RebMab200 and displayed antitumor properties. Short peptides corresponding to the hypervariable complementarity-determining regions (CDRs) of immunoglobulins have been associated with antimicrobial, antiviral, immunomodulatory and antitumor activities regardless of the specificity of the antibody. We have shown that the CDR derived peptide Rb9 induced substrate hyperadherence, inhibition of cell migration and matrix invasion in melanoma and other tumor cell lines...
August 26, 2016: Peptides
https://www.readbyqxmd.com/read/27487150/the-inhibitory-effect-of-7-7-dimethoxyagastisflavone-on-the-metastasis-of-melanoma-cells-via-the-suppression-of-f-actin-polymerization
#19
Ching-Min Lin, Yu-Ling Lin, Shu-Yi Ho, Pin-Rong Chen, Yi-Hsuan Tsai, Chen-Han Chung, Chia-Hsiang Hwang, Nu-Man Tsai, Shey-Cherng Tzou, Chun-Yen Ke, Jung Chang, Yi-Lin Chan, Yu-Shan Wang, Kwan-Hwa Chi, Kuang-Wen Liao
7,7"-Dimethoxyagastisflavone (DMGF), a biflavonoid isolated from Taxus x media cv. Hicksii, induces apoptotic and autophagic cell death. However, whether DMGF suppresses tumor metastasis is unclear. The aim of this study was to investigate the anti-metastatic activities of DMGF on the metastatic processes of melanoma cells in vivo and in vitro. A transwell assay showed that DMGF could effectively attenuate the motility of B16F10 cells, and the results of real-time PCR revealed that DMGF also suppressed the expressions of matrix metalloproteinase-2 (MMP-2)...
July 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27418645/erk-mapk-signaling-drives-overexpression-of-the-rac-gef-prex1-in-braf-and-nras-mutant-melanoma
#20
Meagan B Ryan, Alexander J Finn, Katherine H Pedone, Nancy E Thomas, Channing J Der, Adrienne D Cox
Recently, we identified that PREX1 overexpression is critical for metastatic but not tumorigenic growth in a mouse model of NRAS-driven melanoma. In addition, a PREX1 gene signature correlated with and was dependent on ERK MAPK activation in human melanoma cell lines. In the current study, the underlying mechanism of PREX1 overexpression in human melanoma was assessed. PREX1 protein levels were increased in melanoma tumor tissues and cell lines compared with benign nevi and normal melanocytes, respectively...
October 2016: Molecular Cancer Research: MCR
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