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RECK Controls Breast Cancer Metastasis by Modulating a Convergent, STAT3-dependent Neoangiogenic Switch

ABSTRACT: Metastasis leads to the majority of deaths in breast cancer patients. Here we investigated the molecular and biochemical signaling pathways altered by RECK, a major metastasis suppressor gene in breast cancer. We overexpressed RECK in 2 highly invasive cell lines and knocked-down RECK expression in 2 poorly invasive cell lines. IPA analysis of differentially expressed genes revealed IL-6, and IL8 signaling alteration with RECK pertubation. This lead us to discover that RECK suppresses metastasis and neoangiogenesis at secondary sites by inhibiting STAT3 dependent VEGF & uPA regulating. This finding is significant because it reveals the biology behind a major metastasis suppressor gene in cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE56898 | GEO | 2014/09/01

SECONDARY ACCESSION(S): PRJNA244880

REPOSITORIES: GEO

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RECK Controls Breast Cancer Metastasis by Modulating a Convergent, STAT3-dependent Neoangiogenic Switch

Project description:Metastasis leads to the majority of deaths in breast cancer patients. Here we investigated the molecular and biochemical signaling pathways altered by RECK, a major metastasis suppressor gene in breast cancer. We overexpressed RECK in 2 highly invasive cell lines and knocked-down RECK expression in 2 poorly invasive cell lines. IPA analysis of differentially expressed genes revealed IL-6, and IL8 signaling alteration with RECK pertubation. This lead us to discover that RECK suppresses metastasis and neoangiogenesis at secondary sites by inhibiting STAT3 dependent VEGF & uPA regulating. This finding is significant because it reveals the biology behind a major metastasis suppressor gene in cancer. Cell lines were obtained from the ATCC or were generous gifts from Dr Joan Massague (MSKCC). Invasive cell lines were stably infected with a constitutively expressing RECK construct or and Empty Vector control. Poorly invasive cell lines were transfected with a Scramble siRNA or siRNA targeting the RECK gene. RNA was extracted using the RNeasy kit (Qiagen) as per the manufacturer’s instructions. Expression analysis was performed using the Affymetrics U133 2.0 microarray (Affymetrix). Affymetrix CEL files were imported into the Partek Genomics Suite (Partek).

2014-09-01 | E-GEOD-56898 | biostudies-arrayexpress

Expression changes following siRNA knockdown of ADRM1 in ovarian cell line OAW42

Project description:Knock-down of ovarian cancer amplification target ADRM1 leads to down regulation of GIPC1 and up-regulation of RECK. Among 20q13-amplified genes in ovarian cancer, ADRM1 overexpression was the most highly correlated with amplification, and was significantly upregulated with respect to stage, recurrence and metastasis. In addition, overexpression of ADRM1 correlated significantly with shorter time to recurrence and overall survival. Herein, array-CGH and microarray expression of ovarian cancer cell lines, provides evidence consistent with the primary tumor data that ADRM1 is a 20q13 amplification target. Knock-down of ADRM1 in amplified ovarian cell line OAW42 results in down-regulation of growth factor GIPC1 and up-regulation of tumor-suppressor RECK RNA and protein. In our dataset of 141 ovarian primary tumors, ADRM1 overexpression significantly correlates with GIPC1 overexpression. In addition, there is a significant anticorrelation between ADRM1 overexpression and RECK expression. Further research is necessary to determine whether targeting knock-down of ADRM1 in 20q13-amplified ovarian cancers results in growth inhibition and tumor suppression via downstream targets GIPC1 and RECK. ADRM1 siRNA treated OAW42 compared directly to untreated or nonspecific RNA treated OAW42

2011-01-14 | E-GEOD-26634 | biostudies-arrayexpress

Expression changes following siRNA knockdown of ADRM1 in ovarian cell line OAW42

2011-01-14 | GSE26634 | GEO

Expression data from RECK-overexpressing HT1080 fibrosarcoma cells

Project description:RECK, a glycosylphosphatidylinositol-anchored glycoprotein, inhibits the enzymatic activities of some matrix metalloproteinases (MMP), thereby suppressing tumor cell metastasis; however, the detailed mechanism is still obscure. In this study, we compared the gene expression profiles between mock- and RECK-transfected HT1080 cells. Three established cell lines were selected for RNA extraction and hybridization on Affymetrix microarrays: (1) mock-transfected HT1080 cells, designated as HT1080-Zeo, (2) RECK-overexpressing HT1080 cells, designated as HT1080-RECK, and (3) RECK/4NQ-overexpressing HT1080 cells (in which four N-glycosylation asparagine residues of RECK (Asn86, Asn200, Asn297, and Asn352) were replaced with glutamine residues), designated as HT1080-RECK/4NQ.

2010-04-14 | E-GEOD-21306 | biostudies-arrayexpress

Synergy between plasminogen activator inhibitor-1 and Snail in tumoral migration

Project description:Snail, a family of transcriptional repressors implicated in cell movement, has been correlated with tumour invasivity. The Plasminogen Activation system (PAs), including urokinase (uPA), its receptor (uPAR), and its inhibitor (PAI-1), also plays a key role in cancer invasion and metastasis, either through proteolytic degradation or by non proteolytic modulation of cell adhesion and migration. Thus, Snail and PAs both influence those processes and are over-expressed in cancers. In this study we aimed to determine first whether Snail activity is correlated with PAs components expression and second how this correlation can influence tumoral cell migration. Keywords: Tumoral migration Comparison the invasive breast cancer cell-line MDA-MB-231 expressing Snail (MDA-Neo) with its derived clone expressing a dominant negative form of Snail (Snail-DN). Expression of PAs mRNAs was performed by cDNA microarrays and real time quantitative RT-PCR. Wound healing assay was used to determine cell migration. PAI-1â??s distribution was assessed by immunostaining.

2010-06-24 | E-GEOD-10395 | biostudies-arrayexpress

Homo sapiens

Project description:RECK Controls Breast Cancer Metastasis by Modulating a Convergent, STAT3-dependent Neoangiogenic Switch

| PRJNA244880 | ENA

Expression data from ELK3 knocked down MDA-MB-231 cell line.

Project description:Triple-negative breast cancer is a highly aggressive tumor subtype that lacks effective therapeutic targets. Here, we show that ELK3 is overexpressed in a subset of breast cancers, in particular basal-like and normal-like/claudin-low cell lines. Suppression of ELK3 in MDA-MB-231 cells led to transdifferentiation from an invasive mesenchymal phenotype to a non-invasive epithelial phenotype both in vitro and in vivo. Suppression of ELK3 results in the extensive changes in genome expression profiles. Among these, GATA3, a master suppressor of metastasis, was epigenetically activated and we found that suppression of GATA3 led to the restoration of migration and invasion. These results suggest that the ELK3-GATA3 axis is a major pathway that promotes metastasis of MDA-MB-231 cells. Retrovirus expressing shRNA of ELK3 was transduced into MDA-MB-231 cell line and stable cell line of which ELK3 is suppressed more than 50% was selected by the drug selection (Puromycin).

2016-06-15 | E-GEOD-83325 | biostudies-arrayexpress

Expression data from ELK3 knocked down MDA-MB-231 cell line.

2016-06-15 | GSE83325 | GEO

BRMS1L suppresses breast cancer metastasis by inducing epigenetic silence of FZD10

Project description:BRMS1L (breast cancer metastasis suppressor 1 likeM-oM-<M-^LBRMS1-like) is a component of the SIN3A-HDAC corepressor complex that suppresses target gene transcription. Here, we show that reduced BRMS1L in breast cancer tissues is associated with tumor metastasis and poor patient survival. Functionally, BRMS1L inhibits migration and invasion of breast cancer cells by inhibiting epithelial-mesenchymal transition (EMT). These effects are mediated by epigenetic silencing of FZD10, a receptor for Wnt signaling, by facilitating the recruitment of HDAC1 to its promoter and enhancing histone H3K9 deacetylation. Consequently, BRMS1L-induced FZD10 silencing inhibits aberrant activation of WNT3-FZD10-M-oM-^AM-"-catenin signaling. Furthermore, BRMS1L is a target of miR-106b and miR-106b upregulation leads to BRMS1L reduction in breast cancer cells. RNAi-mediated silencing of BRMS1L expression promotes metastasis of breast cancer xenografts in immunocompromised mice, while ectopic BRMS1L expression inhibits metastasis. Therefore, BRMS1L provides an epigenetic regulation of Wnt signaling in breast cancer cells and acts as a breast cancer metastasis suppressor. Ther transfection analysis used here were further desxribed in Chang Gong, eta al.2013. miR-106b expression determines the proliferation paradox of TGF-M-NM-2 in breast cancer cells. Oncogene. 2013 A two chip study using total RNA recovered from MDA-MB-231 breast cancer cells transfected with negative control vector or vector overexpressing BRMS1L for 24 hours. Each chip measures the expression 45033 genes were collected from the authoritative data source including NCBI.

2014-09-12 | E-GEOD-61354 | biostudies-arrayexpress

Copy number profiling of synchronous primary and metastasis of invasive breast cancer

Project description:We sought to define the repertoire of genetic alterations in synchronous primary and metastasis of invasive breast cancer

2017-01-31 | GSE80806 | GEO