Ran promotes membrane targeting and stabilization of RhoA to orchestrate ovarian cancer cell invasion

Zaoui, Kossay; Boudhraa, Zied; Khalifé, Paul; Carmona, Eurı́dice; Provencher, Diane; Mes‐Masson, Anne‐Marie

doi:10.1038/s41467-019-10570-w

Cited by 41 publications

(33 citation statements)

References 58 publications

(75 reference statements)

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“…Previous research has shown that altered expression of particular genes may affect ESCC cell metastasis, invasion, apoptosis and proliferation [15][16][17] . Our results agree with the fact that carcinoma cell metastasis and invasion are closely associated with abnormal cell adhesion, endodermal cell division and nuclear division [18][19][20] . Extracellular matrix (ECM), is a critical component of the cancer cell niche, it can provide the tissue with the mechanical support and also mediate the cell-microenvironment interactions 21,22 .…”

Section: Discussionsupporting

confidence: 92%

Identification of candidate aberrantly methylated and differentially expressed genes in Esophageal squamous cell carcinoma

Han

Yang

Hosseini

et al. 2020

Sci Rep

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Aberrant methylated genes (DMGs) play an important role in the etiology and pathogenesis of esophageal squamous cell carcinoma (ESCC). In this study, we aimed to integrate three cohorts profile datasets to ascertain aberrant methylated-differentially expressed genes and pathways associated with ESCC by comprehensive bioinformatics analysis. We downloaded data of gene expression microarrays (GSE20347, GSE38129) and gene methylation microarrays (GSE52826) from the Gene Expression Omnibus (GEO) database. Aberrantly differentially expressed genes (DEGs) were obtained by GEO2R tool. The David database was then used to perform Gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome pathway enrichment analyses on selected genes. STRING and Cytoscape software were used to construct a protein-protein interaction (PPI) network, then the modules in the PPI networks were analyzed with MCODE and the hub genes chose from the PPI networks were verified by Oncomine and TCGA database. In total, 291 hypomethylation-high expression genes and 168 hypermethylation-low expression genes were identified at the screening step, and finally found six mostly changed hub genes including KIF14, CDK1, AURKA, LCN2, TGM1, and DSG1. Pathway analysis indicated that aberrantly methylated DEGs mainly associated with the P13K-AKT signaling, cAMP signaling and cell cycle process. After validation in multiple databases, most hub genes remained significant. Patients with high expression of AURKA were associated with shorter overall survival. To summarize, we have identified six feasible aberrant methylated-differentially expressed genes and pathways in ESCC by bioinformatics analysis, potentially providing valuable information for the molecular mechanisms of ESCC. Our data combined the analysis of gene expression profiling microarrays and gene methylation profiling microarrays, simultaneously, and in this way, it can shed a light for screening and diagnosis of ESCC in future. Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide, with incidence rates ranking fourth and eighth in China and worldwide, respectively 1,2. ESCC is a serious threat to human health, and its five-year survival rate is less than 10%, making it a leading cause of cancer-related death 3. So far,

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Section: Discussionsupporting

confidence: 92%

Identification of candidate aberrantly methylated and differentially expressed genes in Esophageal squamous cell carcinoma

Han

Yang

Hosseini

et al. 2020

Sci Rep

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“…The migration and invasion assays have shown that A375 hEVs but not nEVs induced invasion of A375 cells and NHDFs compared to A375 nEVs, while 501Mel hEVs increased invasion of NHDFs at early time points only. This could be due to the increased expression of PRMT5 in the melanoma hEVs, as PRMT5 well as RNA have recently been shown to regulate cancer cell invasion [72][73][74]. Here, we did not observe an effect of nEVs or hEVs on proliferation in normoxic conditions, whereas Patton et al have recently shown that hEVs derived from pancreatic cancer cells can promote proliferation, however under hypoxia [75].…”

Section: Discussioncontrasting

confidence: 75%

Hypoxia-Induced Adaptations of miRNomes and Proteomes in Melanoma Cells and Their Secreted Extracellular Vesicles

Walbrecq

Lecha

Gaigneaux

et al. 2020

Cancers

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Reduced levels of intratumoural oxygen are associated with hypoxia-induced pro-oncogenic events such as invasion, metabolic reprogramming, epithelial–mesenchymal transition, metastasis and resistance to therapy, all favouring cancer progression. Small extracellular vesicles (EV) shuttle various cargos (proteins, miRNAs, DNA and others). Tumour-derived EVs can be taken up by neighbouring or distant cells in the tumour microenvironment, thus facilitating intercellular communication. The quantity of extracellular vesicle secretion and their composition can vary with changing microenvironmental conditions and disease states. Here, we investigated in melanoma cells the influence of hypoxia on the content and number of secreted EVs. Whole miRNome and proteome profiling revealed distinct expression patterns in normoxic or hypoxic growth conditions. Apart from the well-known miR-210, we identified miR-1290 as a novel hypoxia-associated microRNA, which was highly abundant in hypoxic EVs. On the other hand, miR-23a-5p and -23b-5p were consistently downregulated in hypoxic conditions, while the protein levels of the miR-23a/b-5p-predicted target IPO11 were concomitantly upregulated. Furthermore, hypoxic melanoma EVs exhibit a signature consisting of six proteins (AKR7A2, DDX39B, EIF3C, FARSA, PRMT5, VARS), which were significantly associated with a poor prognosis for melanoma patients, indicating that proteins and/or miRNAs secreted by cancer cells may be exploited as biomarkers.

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“…Ran can form a complex with RhoA, leading to RhoA stabilization and activation. This Ran-RhoA signaling complex could be a molecular target for controlling cancer metastasis [ 128 ].…”

Section: Functional Pathways Affected By Oc Fitness Genesmentioning

confidence: 99%

An Overview of Candidate Therapeutic Target Genes in Ovarian Cancer

Alexandrova

Pecoraro

Sellitto

et al. 2020

Cancers

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Ovarian cancer (OC) shows the highest mortality rate among gynecological malignancies and, because of the absence of specific symptoms, it is frequently diagnosed at an advanced stage, mainly due to the lack of specific and early biomarkers, such as those based on cancer molecular signature identification. Indeed, although significant progress has been made toward improving the clinical outcome of other cancers, rates of mortality for OC are essentially unchanged since 1980, suggesting the need of new approaches to identify and characterize the molecular mechanisms underlying pathogenesis and progression of these malignancies. In addition, due to the low response rate and the high frequency of resistance to current treatments, emerging therapeutic strategies against OC focus on targeting single factors and pathways specifically involved in tumor growth and metastasis. To date, loss-of-function screenings are extensively applied to identify key drug targets in cancer, seeking for more effective, disease-tailored treatments to overcome lack of response or resistance to current therapies. We review here the information relative to essential genes and functional pathways recently discovered in OC, often strictly interconnected with each other and representing promising biomarkers and molecular targets to treat these malignancies.

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Ran promotes membrane targeting and stabilization of RhoA to orchestrate ovarian cancer cell invasion

Cited by 41 publications

References 58 publications

Identification of candidate aberrantly methylated and differentially expressed genes in Esophageal squamous cell carcinoma

Identification of candidate aberrantly methylated and differentially expressed genes in Esophageal squamous cell carcinoma

Hypoxia-Induced Adaptations of miRNomes and Proteomes in Melanoma Cells and Their Secreted Extracellular Vesicles

An Overview of Candidate Therapeutic Target Genes in Ovarian Cancer

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