Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA218205 | ENA |
REPOSITORIES: ENA
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Project description:Alpha-parvin (PARVA) is known to involve in the linkage of integrins, regulation of actin cytoskeleton dynamics, and cell survival. However, the role of PARVA in cancer progress is still unclear. Here, we identify PARVA as a potential oncogene from a lung cancer invasion cell line model by expression microarrays. Overexpression of PARVA enhances cell invasion, colony formation ability, and endothelial cell tube formation but knockdown of PARVA inhibits invasion and tube formation in vitro. PARVA also promotes tumorigenicity, angiogenesis, metastasis and mortality by in vivo tumorigenesis and metastasis mouse models. To explore the underlying mechanism, the PARVA-regulated signaling pathways were analyzed in PARVA-overexpressing cells compare with mock controls by expression microarrays. We used microarrays to profile the global gene expression of PARVA-overexpressing cells compared with mock control cells and identified the pathways involved in PARVA-induced biofunctional alterations.
2016-08-25 | GSE50657 | GEO
Project description:Lung cancer is the leading cause of cancer deaths. Its high mortality is associated with high metastatic potential. Here, we show that the RAC1-selective guanine nucleotide exchange factor T cell invasion and metastasis-inducing protein 1 (TIAM1) promotes cell migration and invasion in the most common subtype of lung cancer, non-small-cell lung cancer (NSCLC), through an unexpected nuclear function. We show that TIAM1 interacts with TRIM28, a master regulator of gene expression, in the nucleus of NSCLC cells. We reveal that a TIAM1-TRIM28 complex promotes epithelial-to-mesenchymal transition, a phenotypic switch implicated in cell migration and invasion. This occurs through H3K9me3-induced silencing of protocadherins and by decreasing E-cadherin expression, thereby antagonizing cell–cell adhesion. Consistently, TIAM1 or TRIM28 depletion suppresses the migration of NSCLC cells, while migration is restored by the simultaneous depletion of protocadherins. Importantly, high nuclear TIAM1 in clinical specimens is associated with advanced-stage lung adenocarcinoma, decreased patient survival, and inversely correlates with E-cadherin expression.
2023-09-12 | GSE219030 | GEO
Project description:To gain insight into EMT-independent biological processes through which PI3K promotes invasion, RNA samples from 344SQ_p110α shRNA cells and 344SQ_scr cells were subjected to global transcriptional profiling. Two groups, control and PIK3CA shRNA, in 344SQ lung cancer cell line Two group comparison
2014-05-02 | E-GEOD-46869 | biostudies-arrayexpress
Project description:Oxidative phosphorylation promotes primary melanoma invasion
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Project description:Lung cancer is the leading cause of cancer-related deaths worldwide. Despite advancements and improvements in surgical and medical treatments, the survival rate of lung cancer patients remains frustratingly poor. Local control for early stage non-small cell lung cancer (NSCLC) has dramatically improved over the last decades for both operable and inoperable patients. However, the molecular mechanisms of NSCLC invasion leading to regional and distant disease spread remain poorly understood. Here we identify miR-224 to be significantly up-regulated in NSCLC tissues, in particular in resected NSCLC metastasis. Increased miR-224 expression promotes cell migration, invasion and proliferation by directly targeting the tumor suppressors, TNFAIP1 and SMAD4. In concordance with in vitro studies, mouse xenograft studies validated that miR-224 function as a potent oncomiR in NSCLC in vivo. Moreover, we found promoter hypomethylation and activated ERK signaling to be involved in the regulation of miR-224 expression in NSCLC. Up-regulated mir-224 thus facilitates tumor progression by shifting the equilibrium of the partially antagonist functions of SMAD4 and TNFAIP1 towards enhanced invasion and growth in NSCLC. Our findings indicate that targeting miR-224 could be effective in the treatment of certain lung cancer patients Oncogenic role of miR-224 in lung cancer
2015-07-01 | E-GEOD-64859 | biostudies-arrayexpress
Project description:Vascular pericytes, an important cellular component, in the tumor microenvironment, are often associated with tumor vasculatures and their functions in cancer invasion and metastasis are poorly understood. Here we show that PDGF-BB induces pericyte fibroblast transition (designated as PFT), which significantly contributes to tumor invasion and metastasis. Gain- and loss-of-function experiments demonstrate that the PDGF-BB-PDGFRβ signaling promotes PFT in vitro and in in vivo tumors. Genome-wide expression analysis indicates that PDGF-BB-activated pericytes acquire mesenchymal progenitor features. Pharmacological inhibition and genetic deletion of PDGFRβ ablate the PDGF-BB-induced PFT. Genetic tracing of pericytes with two independent mouse strains, i.e., TN-AP-CreERT2:R26R-tdTomato and NG2:R26R-tdTomato, shows that PFT cells gains stromal fibroblast and myofibroblast markers in tumors. Importantly, co-implantation of PFT cells with less-invasive tumor cells in mice markedly promotes tumor dissemination and invasion, leading to an increased number of circulating tumor cells (CTCs) and metastasis. Our findings reveal a novel mechanism of vascular pericytes in PDGF-BB-promoted cancer invasion and metastasis by inducing PFT and thus targeting PFT may offer a new treatment option of cancer metastasis. Pericytes were isolated and treated with PDGF-BB or control for 1 or 5 days
2016-08-24 | E-GEOD-85955 | biostudies-arrayexpress
Project description:The Fra-1 transcription factor promotes tumor cell growth, invasion and metastasis. While characterizing five breast cancer cell lines derived from primary human breast tumors, we identified BRC-31 as a novel basal-like cell model that expresses elevated Fra-1 levels. BRC-31 cells display elevated FAK, SRC and ERK2 phosphorylation relative to luminal breast cancer models. Inhibition of this signaling axis, through the use of pharmacological inhibitors, reduces the phosphorylation and stabilization of Fra-1. Elevated integrin αVβ3 expression in these cells suggested that integrin receptors might activate this FAK-SRC-ERK2 signaling axis to enhance Fra-1 phosphorylation. These cells also express high levels of uPAR, a GPI-anchored receptor that has been shown to enhance integrin-mediated signaling initiated by Vitronectin engagement. Transient knockdown of uPAR in BRC31 cells grown on Vitronectin reduces Fra-1 phosphorylation and stabilization and uPAR and Fra-1 are required for Vitronectin-induced cell invasion. In clinical samples, a molecular component signature consisting of Vitronectin-uPAR-uPA-Fra-1 predicts poor overall survival in patients with breast cancer and correlates with a Fra-1 transcriptional signature. Taken together, we have identified a novel-signaling axis that leads to phosphorylation and stabilization of Fra-1, a transcription factor that is emerging as an important modulator of breast cancer progression and metastasis.
2017-08-03 | GSE69915 | GEO
Project description:LMTK3 is an oncogenic receptor tyrosine kinase (RTK) implicated in various types of cancer including breast, lung, gastric and colorectal. It is localized in different cellular compartments but its nuclear function has not been investigated thus far. We have mapped LMTK3 binding across the genome using ChIP-seq and found that LMTK3 binding events are correlated with repressive chromatin markers. We further identified KRAB associated protein-1 (KAP1) as a novel binding partner of LMTK3. The LMTK3/KAP1 interaction is stabilized by PP1_, which suppresses KAP1 phosphorylation specifically at LMTK3-associated chromatin regions, inducing chromatin condensation and resulting in transcriptional repression of LMTK3-bound tumour suppressor-like genes. Furthermore, LMTK3 functions at enhancer regions in tethering the chromatin to the nuclear periphery, resulting in H3K9me3 modification and gene silencing. In summary, we propose a new model where a scaffolding function of nuclear LMTK3 promotes cancer progression through chromatin remodeling, revealing a new mechanism of RTK activity. Examination of LMTK3 binding profile in 2 cell types.
2015-06-30 | E-GEOD-70385 | biostudies-arrayexpress
Project description:Lung cancer is one of the most common cancers in the world, which accounts for about 27% of all cancer deaths. However, the mechanisms underlying the pathogenesis of lung cancer cells remain largely elusive. In this study, we examined the role of the Forkhead box protein P1 (FOXP1) in lung cancer development. Our Oncomine analysis shows that FOXP1 is downregulated in lung adenocarcinoma compared with normal lung tissue. Knockdown of FOXP1 promotes the proliferation growth and invasion of PC9 and A549 cells by regulating genes of chemokine signaling molecules, including CCR1, ADCY5, GNG7, VAV3, and PLCB1. Simultaneous knockdown of CCR1 and FOXP1 attenuated FOXP1 knockdown-induced increase of lung cancer cell growth. Finally, knockdown of FOXP1 in PC9 cells promotes the tumorigenesis via CCR1 signaling in xenograft mouse model. Taken together, our data suggest that FOXP1 plays important roles in preventing lung adenocarcinoma development via suppressing chemokine signaling pathways. Novel strategies might be developed to prevent the development of lung adenocarcinoma by targeting FOXP1
2018-02-10 | GSE108500 | GEO
Project description:Background: JAG-1 is a ligand of Notch signaling and can regulate cell differentiation and proliferation in cancers. Recent studies indicated that JAG1 is a gene associated with cancer progression. Therefore, we investigated the role of JAG1 in lung cancer progression. Methods: The expression of JAG1 was manipulated by overexpression or RNA silencing in several human lung cell lines. The effect of JAG1 on tumorigenesis and invasion was assessed by the cell anchorage-independent growth, cell proliferation, cell migration and invasion assays in vitro as well as metastasis in vivo. The potential downstream genes of JAG1 were identified by oligonucleotide microarrays and quantitative reverse transcription¡Vpolymerase chain reaction (RT-PCR). We further measured JAG1 expression in lung cancer specimens by RT-PCR. Correlation between JAG1 expression and overall survival of lung cancer patients was determined by using the log-rank test and multivariable Cox proportional hazards regression analysis. All statistical tests were two-sided. Results: JAG1 enhanced anchorage-independent growth, cell migration, invasion in the lower invasive cells, CL1-0. JAG1 also increased the capability of migration and invasion in the other two lung cancer cell lines (A549 and NCI-H226). The silencing of JAG1 inhibited migration and invasion activities of the higher invasive cells, CL1-5, by siRNA technology. The invasion-promoting activity of JAG1 was also demonstrated in vivo by using a mouse metastasis model. By microarray analysis, we found that the expression of heat shock 70kDa protein 2 (HSPA2) was activated by JAG1 overexpression and eliminated by JAG1 silencing. Moreover, lung cancer patients with high JAG1 expressing tumors had shorter overall survival than those with low-expressing tumors. Conclusion: JAG1 might be an oncogene which promotes colonogenesis and metastasis, and high JAG1 expression is associated with shorten survival in lung cancer. In this investigation, we used a lung cancer invasion cell model to identify the genes involved in cancer progression. JAG1 is a potential oncogene whose expression is correlated to the survival of patients with breast, prostate and liver cancers. However, the role of JAG1 in lung caner progression has not been reported, particularly in metastasis. Here, JAG1 was ectopically expressed in lower invasive lung cancer cell line its impact on colonogenesis, migration and invasiveness was assessed. The underlying mechanism was explored by JAG1-expressed transfectants and microarrays and the clinical relevance was evaluated by quantitative RT-PCR.
2013-01-12 | E-GEOD-14995 | biostudies-arrayexpress