Explore the role of RHAMM in invasion/metastasis of breast cancer
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PROVIDER: PRJNA932850 | ENA |
REPOSITORIES: ENA
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Project description:To understand the mechanism of breast cancer invasion and metastasis, we collected tumor tissue from a cohort of 120 breast cancer patients and performed a Nanostring gene profiling assay (26 cases were removed from further analysis during quality control). Differential gene expression (DGE) analysis was done by comparing patients with/without lymph node metastasis lymph nodes. To explore the role of RHAMM in breast cancer invasion and metastasis, we created an RHAMM Related Signature (RRS) by intersecting the top 50 genes with another DGE list generated from a murine model wherein overexpression of an oncogenic RHAMM isoform increased cell motility in vivo tumor engraftment, and metastasis to identify RHAMM-related transcriptome changes specifically.
2023-03-17 | GSE224883 | GEO
Project description:The role of HK2 in breast cancer metastasis
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Project description:Purpose: The BET family protein BRD4 is an important anti-tumor target and is highly expressed in breast cancer. However, BET inhibitors are susceptible to drug resistance. The aim of this study is to explore the mechanism of BET inhibitor JQ-1 combined with cardamonin in the anti-invasion and metastasis of triple-negative breast cancer. Methods: triple-negative breast cancer cells mRNA of DMSO (Control), JQ-1,cardamonin and combined groups were progressed with deep sequencing, in triplicate through Illumina sequencing platform (HiSeqTM 2500). Genes with adjusted P-value < 0.01 and |foldChange| > 2 were defined as differentially expressed genes (DEGs) and subjected to the following GO and KEGG enrichment. qRT-PCR was performed to validate several essential genes using QuantStudio 5 (Thermo Fisher) and SYBR Green assays. Results: As an inhibitor of mTOR, Cardamonin(CAR) can inhibit the proliferation of tumors. Research have found that BET inhibitor can affect the function of a large number of genes by regulating the epigenome, which plays an important role in a variety of diseases. In this study we explored the JQ1 which is a BRD4 protein inhibitor can inhibit the proliferation and metastasis of MDA-MB-231 cells in triple-negative breast cancer cell lines, and this phenomenon can be significantly enhanced when CAR is combined with JQ-1, and the same results are shown in mouse tumor formation experiments and triple-negative breast cancer organoids. At the same time, RNA-seq was performed in MD1-MB-231 cells to explore the changes of specific molecular signaling pathways. We have mapped over 40 million sequence reads to the MDA-MB-231 cell line genome in each specimen.Compared with the control group, CAR and JQ1, the combination group has significantly enriched gene expression. KEGG and GO enrichment analysis indicate that the combination group showed a series of biological processes such as macroautophagy, negative regulation of cell growth, lipid catabolic process, which led to decreased cell viability and decreased proliferation and metastasis ability. Conclusions: In this study, we demonstrated that JQ-1 combined with cardamomin could inhibit the invasion and metastasis of triple-negative breast cancer MDA-MB-231 cells, induce cell cycle arrest and promote cell apoptosis. The results of RNA-Seq were consistent with our in vitro and in vivo experiments, which demonstrated that the combination of JQ-1 and cardamonin effectively inhibited the proliferation, invasion and metastasis of MDA-MB-231 cells.
2024-01-01 | GSE236250 | GEO
Project description:Cancer/testis Antigen-Plac1 Promotes Invasion and Metastasis of Breast Cancer
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Project description:PLAC1, cancer-testis antigen, is a crucial element in tumorigenesis and development programs for many cancers. Overexpression of PLAC1 promoted invasion and metastasis of breast cancer cells in vitro and in vivo. Co-immunoprecipitation and immunofluorescence cell staining assays be used revealed that PLAC1 physically interact with Furin to degrade Notch1 and generate NICD (Notch1 intracellar domain) and further inhibit Pten, which is also supported by the microarray analysis.
2018-12-25 | GSE104070 | GEO
Project description:Metastasis is a major cause leading to mortality for lung cancer patients. We identified YWHAZ as a potential metastasis-promoting candidate and found that overexpression of YWHAZ promotes lung cancer cell proliferation, anchorage-independent growth, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo. It not only increases cell protrusions and branchings but also induces epithelial-mesenchymal transition. Most importantly, YWHAZ protein could prevent £]-catenin from ubiquitination via its association with £]-catenin and enhance slug transcriptional activity which is regulated by £]-catenin/TCF signaling pathway. Moreover, YWHAZ expression was higher in tumors than in adjacent normal tissues in 63 Non-small-cell lung cancer (NSCLC) patients. NSCLC patients with high YWHAZ expressing tumors had shorter overall survival than those with low-expressing tumors. We conclude that YWHAZ play a critical role in promoting NSCLC metastasis. In this investigation, we used a lung cancer invasion cell model to identify the genes involved in cancer progression. YWHAZ is a potential oncogene whose expression is correlated to the survival of patients with breast, prostate and liver cancers. However, the role of YWHAZ in lung caner progression has not been reported, particularly in metastasis. Here, YWHAZ 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 YWHAZ-expressed transfectants and microarrays and the clinical relevance was evaluated by quantitative RT-PCR.
2012-11-07 | E-GEOD-20318 | biostudies-arrayexpress
Project description:E-cadherin (E-cad) mediates cell-cell adhesion and has been proposed to suppress both invasion and metastasis. However, invasive ductal cancers retain E-cad expression in the primary tumor, circulating tumor cells, and distant metastases. We recently demonstrated that cancer cell clusters are efficient metastatic seeds. Since clusters organize through cell-cell adhesion, we tested the requirement for E-cad in genetically engineered mouse models of luminal and basal breast cancer. Loss of E-cad increased invasion and dissemination in 3D culture and in the mammary gland. However, E-cad loss also reduced cancer cell proliferation, survival, tumor cell seeding, and metastatic outgrowth in the lungs. At the transcript level, loss of E-cad was associated with increased apoptosis. Consistent with these results, inhibition of apoptosis partially rescued the metastatic phenotype of E-cad null cancer cells. We therefore propose that E-cad is an invasion suppressor, survival factor, and metastasis promoter in invasive ductal cancers.
2019-06-24 | GSE114011 | GEO
Project description:Efforts to improve the clinical outcome of highly aggressive triplenegative breast cancer (TNBC) have been hindered by the lack of effective targeted therapies. Hence, it is important to identify the specific gene targets/pathways driving the invasive phenotype to develop more effective therapeutics. Here we show that UBASH3B (ubiquitin associated and SH3 domain containing B), a protein tyrosine phosphatase, is overexpressed in TNBC, where it supports malignant growth, invasion and metastasis in large through modulating EGFR. We also show that UBASH3B is a functional target of anti-invasive miR-200a that is downregulated in TNBC. Importantly, the oncogenic potential of UBASH3B is dependent on its tyrosine phosphatase activity, which targets CBL ubiquitin ligase for dephosphorylation and inactivation, leading to EGFR upregulation. Thus, UBASH3B may function as a crucial node in bridging multiple invasion-promoting pathways, thus providing a potential new therapeutic target for TNBC. Breast cancer tissues and breast cancer cell lines
2013-06-01 | E-GEOD-36693 | biostudies-arrayexpress
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
Project description:Metastasis initiates when cancer cells escape from the primary tumor, which requires changes to intercellular junctions. Claudins are transmembrane proteins that form the tight junction, and their expression is reduced in aggressive breast tumors. However, claudins’ roles during breast cancer metastasis remain unclear. We used gain- and loss-of-function genetics in organoids isolated from murine breast cancer models to establish that Cldn7 suppresses invasion and metastasis. Transcriptomic analysis revealed that Cldn7 knockdown induced smooth muscle actin (SMA)-related genes and a broader mesenchymal phenotype. We validated our results in human cell lines, fresh human tumor tissue, bulk RNA-seq, and public single cell RNA-seq data. We consistently observed an inverse relationship between Cldn7 expression and expression of SMA-related genes. Furthermore, knockdown and overexpression of SMA-related genes demonstrated that they promote breast cancer invasion. Our data reveal that Cldn7 suppresses breast cancer invasion and metastasis through negative regulation of SMA-related and mesenchymal gene expression.
2024-09-13 | GSE273512 | GEO