Ras-Association Domain Family 1C Protein Promotes Breast Cancer Cell Migration
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: xinmin Li
PROVIDER: E-GEOD-24473 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:RASSF1C, unlike RASSF1A, is not a tumor suppressor, but instead may play a role in stimulating metastasis and survival in breast cancer cells RASSF1C over-expression enhances T47D cell invasion/migration in vitro
2010-10-02 | GSE24473 | GEO
Project description:RASSF1C, unlike RASSF1A, is not a tumor suppressor, but instead may play a role in stimulating metastasis and survival in breast cancer cells RASSF1C over-expression enhances T47D cell invasion/migration in vitro Three RASSF1C over-expression samples vs three controls
| S-ECPF-GEOD-24473 | biostudies-other
Project description:BACKGROUND: The Ras association domain family 1 (RASSF1) gene is a Ras effector encoding two major mRNA forms, RASSF1A and RASSF1C, derived by alternative promoter selection and alternative mRNA splicing. RASSF1A is a tumor suppressor gene. However, very little is known about the function of RASSF1C both in normal and transformed cells. METHODS: Gene silencing and over-expression techniques were used to modulate RASSF1C expression in human breast cancer cells. Affymetrix-microarray analysis was performed using T47D cells over-expressing RASSF1C to identify RASSF1C target genes. RT-PCR and western blot techniques were used to validate target gene expression. Cell invasion and apoptosis assays were also performed. RESULTS: In this article, we report the effects of altering RASSF1C expression in human breast cancer cells. We found that silencing RASSF1C mRNA in breast cancer cell lines (MDA-MB231 and T47D) caused a small but significant decrease in cell proliferation. Conversely, inducible over-expression of RASSF1C in breast cancer cells (MDA-MB231 and T47D) resulted in a small increase in cell proliferation. We also report on the identification of novel RASSF1C target genes. RASSF1C down-regulates several pro-apoptotic and tumor suppressor genes and up-regulates several growth promoting genes in breast cancer cells. We further show that down-regulation of caspase 3 via overexpression of RASSF1C reduces breast cancer cells' sensitivity to the apoptosis inducing agent, etoposide. Furthermore, we found that RASSF1C over-expression enhances T47D cell invasion/migration in vitro. CONCLUSION: Together, our findings suggest that RASSF1C, unlike RASSF1A, is not a tumor suppressor, but instead may play a role in stimulating metastasis and survival in breast cancer cells.
| S-EPMC2965177 | biostudies-literature
Project description:The tumor suppressor gene RASSF1A (Ras association domain family protein 1A) coding for a microtubule stabilizing protein is epigenetically silenced in most human cancers. As a binding partner of the kinases MST1 and MST2, the mammalian orthologues of the Drosophila Hippo kinase, RASSF1A is a potential regulator of the Hippo tumor suppressor pathway. RASSF1A shares these properties with the scaffold protein SAV1. The role of this pathway in human cancer has remained enigmatic because Hippo pathway components are rarely mutated. Rassf1a homozygous knockout mice developed liver tumors. However, heterozygous deletion of Sav1 or co-deletion of Rassf1a and Sav1 produced liver tumors with much higher efficiency than single deletion of Rassf1a. Analysis of RASSF1A binding partners by mass spectrometry identified the Hippo kinases MST1, MST2 and the oncogenic IkB kinase TBK1 as the most significantly enriched RASSF1A-interacting proteins. The transcriptome of Rassf1a-/- livers was more deregulated than that of Sav1+/- livers and the transcriptome of Rassf1a-/-, Sav1+/- livers was similar to that of Rassf1a-/- mice. We found that the levels of Tbk1 protein were substantially upregulated in livers lacking Rassf1a, and at the transcript level, factors regulating Tbk1 stability, including Usp2 and Dtx4, were also dysregulated. Furthermore, transcripts of several beta tubulin isoforms were increased in the Rassf1a-deficient liver genotypes presumably reflecting a role of Rassf1a as a tubulin-binding and microtubule-stabilizing protein. Our data suggest a multifactorial role of Rassf1a in suppression of liver carcinogenesis.
2016-05-31 | GSE73911 | GEO
Project description:The tumor suppressor gene RASSF1A (Ras association domain family protein 1A) coding for a microtubule stabilizing protein is epigenetically silenced in most human cancers. As a binding partner of the kinases MST1 and MST2, the mammalian orthologues of the Drosophila Hippo kinase, RASSF1A is a potential regulator of the Hippo tumor suppressor pathway. RASSF1A shares these properties with the scaffold protein SAV1. The role of this pathway in human cancer has remained enigmatic because Hippo pathway components are rarely mutated. Rassf1a homozygous knockout mice developed liver tumors. However, heterozygous deletion of Sav1 or co-deletion of Rassf1a and Sav1 produced liver tumors with much higher efficiency than single deletion of Rassf1a. Analysis of RASSF1A binding partners by mass spectrometry identified the Hippo kinases MST1, MST2 and the oncogenic IkB kinase TBK1 as the most significantly enriched RASSF1A-interacting proteins. The transcriptome of Rassf1a-/- livers was more deregulated than that of Sav1+/- livers and the transcriptome of Rassf1a-/-, Sav1+/- livers was similar to that of Rassf1a-/- mice. We found that the levels of Tbk1 protein were substantially upregulated in livers lacking Rassf1a, and at the transcript level, factors regulating Tbk1 stability, including Usp2 and Dtx4, were also dysregulated. Furthermore, transcripts of several beta tubulin isoforms were increased in the Rassf1a-deficient liver genotypes presumably reflecting a role of Rassf1a as a tubulin-binding and microtubule-stabilizing protein. Our data suggest a multifactorial role of Rassf1a in suppression of liver carcinogenesis. Analysis of gene expression in liver of wildtype 129 mice, Rassf1a-/- mice (RA), Sav1+/- mice (SA) and Rassf1a-/- Sav1+/- mice (RA_SA)
2016-05-31 | E-GEOD-73911 | biostudies-arrayexpress
Project description:Several groups reported the correlation between hypermethylation of RASSF1A and aggressiveness or a poor outcome in various pediatric tumors, including Wilms tumor. In addition, it is known that the overexpression of RASSF1A promotes apoptotic cell cycle arrest and reduces the tumorigenicity. In an attempt to identify epigenetic targets related to the biological features of rhabdoid tumor of the kidney (RTK), we analyzed the methylation level of the RASSF1A gene in RTK. RASSF1A promoter region in RTK is hypermethylated and the gene and protein expression levels were low. To examine the effect of re-expression of RASSF1A in RTK cells from the viewpoint of gene expression, we performed micro array analysis. We observed neither clear apoptosis induction nor cell-cycle arrest in RASSF1A-expressed RTK cell lines. Furthermore, the geneexpression profiling induced by RASSF1A expression in RTK cell line is curious, and CDK6 expression was significantly increased while CDKN2A expression was significantly decreased after RASSF1A expression. The changes in the gene expression profile that we observed in RTK cells after RASSF1A expression may not be causative events involving the suppression of cell proliferation, but rather antagonizingevents reflecting cellular responses against RASSF1A expression in RTK cells that are deficient in SMARCB1.
2024-04-05 | GSE171508 | GEO
Project description:RASSF1A encodes a tumor suppressor that inhibits RAS’RAF’MEK’ERK signaling and is one of the most frequently inactivated genes in human cancers. MUC1-C is an oncogenic effector of the cancer cell epigenome that is overexpressed in diverse carcinomas. We show here that MUC1-C represses RASSF1A expression in multiple types of KRAS wild-type and mutant cancer cells. Mechanistically, MUC1-C occupies the RASSF1A promoter in a complex with the ZEB1 transcriptional repressor. In turn, MUC1-C/ZEB1 complexes recruit DNA methyltransferase 3b (DNMT3b) to the CpG island in the RASSF1A promoter. Targeting MUC1-C, ZEB1 and DNMT3b thus decreases methylation of the CpG island and derepresses RASSF1A transcription. We also show that targeting MUC1-C downregulates KRAS signaling with decreases in MEK/ERK activation, which is of importance for RAS-mediated tumorigenicity. These findings define a previously unrecognized role for MUC1-C in suppression of RASSF1A and support targeting MUC1-C as an approach for inhibiting KRAS signaling.
2019-05-27 | GSE123860 | GEO
Project description:Modulator of apoptosis 1 (MOAP-1) is a BH3-like protein that plays key roles in both the intrinsic and extrinsic modes of cell death or apoptosis. It is an integral partner to the tumor suppressor Ras association domain family 1A (RASSF1A) and functions to activate the Bcl-2 family pro-apoptotic protein Bax. Although RASSF1A is now considered a bona fide tumor suppressor protein, the role of MOAP-1 as a tumor suppressor is yet to be determined. In this study, we present several lines of evidence from cancer databases, immnoblotting of cancer cells, proliferation and xenograft assays to demonstrate the role of MOAP-1 as a tumor suppressor. MOAP-1 overexpressed tumors display upregulation of multiple genes including several pro-apoptotic members that may influence the role of MOAP-1 in cell death. Frequent loss of MOAP-1 expression, in at least some cancers, appears to be attributed to enhanced proteasomal degradation. The loss of RASSF1A is an early marker of tumorigenesis and we speculate that the additional loss of function of MOAP-1 may be a second âhitâ to functionally compromise the RASSF1A/MOAP-1 death receptor dependent pathway and drive tumorigensis. RNA was isolated mouse xenographs generated with the HCT116 cell line transfected with wild type Myc-tagged MOAP-1, empty Vector or the Myc-tagged MOAP-1 mutants K278R or K264R in triplicate. Pairwise gene expression differences were compared the two samples. Features selected had more than 1.5-fold up-or down-regulated (P values of >05, unpaired Studentâs t-test).
2015-11-02 | E-GEOD-43990 | biostudies-arrayexpress
Project description:Overexpression of high mobility group AT-hook 2 (HMGA2) associated with truncations of its 3’ untranslated region (UTR) with let-7 micro RNA-complementary sequences have been identified in patients with paroxysmal nocturnal hemoglobinuria (PNH). Here, we generated transgenic mice (∆Hmga2 mice) with a 3’UTR-trncated Hmga2 cDNA that overexpress Hmga2 mRNA and protein in hematopoietic organs. ∆Hmga2 mice showed proliferative hematopoiesis that mimicked a myeloproliferative neoplasm (MPN)-like phenotype with increased numbers of all lineages of peripheral blood cells, hypercellular bone marrow (BM), splenomegaly with extramedullary erythropoiesis, and erythropoietin-independent erythroid colony formation compared to wild-type mice. ∆Hmga2 BM-derived cells took over most of hematopoiesis in competitive repopulations during serial BM transplants. When we bred mice with circulating PNH cells (Piga- mice) with ∆Hmga2 mice, the lack of GPI-linked proteins did not add an additional clonal advantage to the ∆Hmga2+ cells. In summary, our results showed that the overexpression of a 3’UTR-truncated Hmga2 leads to a proliferative hematopoiesis with clonal advantage, which may explain clonal expansion in PNH or MPN at the level of HSC. Eight independent preparations of RNA, which included each 2 samples of KLS cells and MEP cells from ∆Hmga2 mice and 2 each from WT mice. Each preparation was made from 4 or 6 mice.
2011-02-06 | E-GEOD-24071 | biostudies-arrayexpress
Project description:We report high-throughput profiling of RBM39 and MLL1 chromatin occupancy; H3K4me3 marks in T47D Control, T47D RBM39 KD and PME cells. By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of RBM39, MLL1 and H3K4me3 in T47D and PME cells. We found that more than 4500 regions were cofound by RBM39 and MLL1.
2021-04-13 | GSE169277 | GEO