Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Knockout of MXRA8 in MDA-MB-231 cells

ABSTRACT: Matrix remodeling associated protein 8 or MXRA8 is a transmembrane protein that can binds arthritogenic alpha viruses like the Chikunggunya virus and provide viral entry into cells. MXRA8 can also interact with integrin β3 and thus possibly regulate cell-cell interactions and binding to the extracellular matrix. While MXRA8 has been associated with reduced survival in patients with colorectal and renal clear cell cancers, the role of MXRA8 in breast cancer remains unexplored. Our previous work exploring genes that mediate the anti-tumor effects of the miR-200c/141 cluster in breast cancer identified MXRA8 as a potential suppressor of breast cancer growth and metastasis. In the current study, MXRA8 was knocked out in the human triple negative breast cancer cell line, MDA-MB-231. Loss of MXRA8 reduce cell proliferation in vitro but had no effect on apoptosis or migration in cultured cells. However, loss of MXRA8 significantly delayed tumor development and reduced metastatic dissemination to the lungs in a xenograft model. RNA sequencing identified three genes, ADMATS1, TIE1, and BMP2 whose expression were significantly reduced in MXRA8 knockout tumors compared to control tumors. MXRA8 staining of a human breast cancer tissue array revealed higher levels of MXRA8 in primary tumors and metastases of aggressive tumor subtypes (TNBC and HER2+) compared to less aggressive, ER+ breast cancers. Our findings demonstrate for the first time that MXRA8 regulates the progression of human TNBC possibly through influencing the interaction of tumor cells with their microenvironment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE238018 | GEO | 2023/09/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Dll1 dependent heterogeneity of tumor and cancer fibroblasts

Project description:To survey the diverse tumor cell populations of aggressive luminal breast cancer (non-TNBC) at a cellular level, we utilized Dll1+ and Dll1- tumors from a recently published PyMT-Dll1mCherry reporter breast cancer mouse model.

2022-08-14 | GSE182011 | GEO

Expression data of patient-derived triple negative breast cancer xenograft tumors

Project description:Triple negative breast cancer (TNBC) is an aggressive subtype that lack targeted clinical therapies. In addition, TNBC is heterogeneous and was recently further sub-classified into seven TNBC subtypes that displayed unique gene expression patterns. To develop therapeutic treatment regimens, we established seven patient-derived xenograft models from TNBC tumors. These xenograft models not only retained the histology and clinical markers of the corresponding patient tumors, but also bearing the same mutations and deletions identified in the patient tumors. Moreover, as part of evaluation of these models, we performed microarrays on the xenograft tumors to assess their TNBC subtypes. After obtaining IRB-approved informed written patient consent, breast cancer tissues were obtained fresh from Stanford Hospital and transplanted into the number 2 mammary fat pads of female NOD SCID mice (NOD.CB17-Prkdcscid/J, Jackson Laboratory West, Sacramento, CA, USA). Mice were maintained in pathogen-free animal housing. The established xenografts were subsequently passaged from mouse to mouse. Xenograft tumor tissues were frozen on dry ice for RNA isolation and microarray analysis.

2014-03-21 | E-GEOD-47079 | biostudies-arrayexpress

Gene expression profiles of triple-negative breast cancer cells under the condition of 3D proliferation

Project description:Triple-negative breast cancer (TNBC) is defined by the absence of estrogen and progesterone receptors and human epidermal growth factor receptor 2, and is the most lethal and aggressive subtype of breast cancer. However, the genes which relate to promote tumor aggressiveness in TNBC remain unclear. In order to investigate specific genes and pathways involved in TNBC tumorigenesis, we compared genes differentially expressed between 3D cultures (3DC) or tumor xenograft models and control two-dimensional cultures (2DC). Total RNA was prepared from the TNBC cells under the condition of 2DC, 3DC and tumor xenograft models, and applied to Affymetrix Human Genome U133 Plus 2.0 Array.

2012-04-30 | E-GEOD-36953 | biostudies-arrayexpress

mRNA differencial expression data between scrambled siRNA-treated mice and HN1L siRNA-treated mice tumor samples

Project description:(HN1L) is a targetable breast cancer stem cell (BCSC) gene that is altered in 25% of whole breast cancer and significantly correlated with shorter overall or relapse-free survival in triple negative breast cancer (TNBC) patients. HN1L silencing reduced the population of BCSCs, inhibited tumor initiation, re-sensitized chemo-resistant tumors to docetaxel, and hindered cancer progression in multiple TNBC cell line derived xenografts. We used microarray to compare mRNA expression profiles from PDX BCM2665 xenograft tumors with or without HN1L knockdown, to identify role of HN1L in regulating cancer stem cells.

2017-12-20 | GSE106106 | GEO

MicroRNA differencial expression data between scrambled siRNA-treated mice and HN1L siRNA-treated mice tumor samples

Project description:(HN1L) is a targetable breast cancer stem cell (BCSC) gene that is altered in 25% of whole breast cancer and significantly correlated with shorter overall or relapse-free survival in triple negative breast cancer (TNBC) patients. HN1L silencing reduced the population of BCSCs, inhibited tumor initiation, re-sensitized chemo-resistant tumors to docetaxel, and hindered cancer progression in multiple TNBC cell line derived xenografts. We used miRNA array to compare miRNA expression profiles from PDX BCM2665 xenograft tumors with or without HN1L knockdown, to identify role of HN1L in regulating miRNA.

2017-12-20 | GSE106199 | GEO

Fatty acid oxidation protects cancer cells from apoptosis through increasing mitochondrial membrane lipids

Project description:<p>Overcoming resistance to chemotherapies remains a major unmet need for cancers such as triple negative breast cancer (TNBC). Therefore, mechanistic studies to provide insight for drug development are urgently needed to overcome TNBC therapy resistance. Recently, an important role of fatty acid β-Oxidation (FAO) in chemoresistance has been shown. But how FAO might mitigate tumor cell apoptosis by chemotherapy is unclear. Here, we show that elevated FAO activates STAT3 by acetylation via elevated acetyl-CoA. Acetylated STAT3 upregulates expression of long-chain acyl-CoA synthetase 4 (ACSL4), resulting in increased phospholipid synthesis. Elevating phospholipids in mitochondrial membranes leads to heightened mitochondrial integrity, which in turn overcomes chemotherapy-induced tumor cell apoptosis. Conversely, in both cultured tumor cells and xenograft tumors, enhanced cancer cell apoptosis by inhibiting ASCL4 or specifically targeting acetylated-STAT3 is associated with a reduction in phospholipids within mitochondrial membranes. This study demonstrates a critical mechanism underlying tumor cell chemoresistance.</p>

2022-05-31 | MTBLS4709 | MetaboLights

Transcriptome profiling of tumors from Kenyan triple negative breast cancer (TNBC) patients.

Project description:Triple negative breast cancer is an aggressive phenotypic breast cancer characterized by ER negative, PR negative and Her2 negative immunohistochemistry status. We embarked on a study to explore the transcriptome of Kenyan TNBC patients and identify potential biomarkers specific to Kenyan population. The transcriptome sequencing of tumors from Kenyan TNBC patients and comparisons with African American and Caucasian TNBC transcriptomes revealed several interesting targets and dysregulated pathways.

2021-04-28 | GSE142258 | GEO

Genomic Regulation of Invasion by STAT3 in Triple Negative Breast Cancer

Project description:Breast cancer is a heterogeneous disease comprised of four molecular subtypes defined by whether the tumor-originating cells are luminal or basal epithelial cells. Breast cancers arising from the luminal mammary duct often express estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor 2 (HER2). Tumors expressing ER and/or PR are treated with anti-hormonal therapies, while tumors overexpressing HER2 are targeted with monoclonal antibodies. Immunohistochemical detection of ER, PR, and HER2 receptors/proteins is a critical step in breast cancer diagnosis and guided treatment. Breast tumors that do not express these proteins are known as “triple negative breast cancer” (TNBC) and are typically basal-like. TNBCs are the most aggressive subtype, with the highest mortality rates and no targeted therapy, so there is a pressing need to identify important TNBC tumor regulators. The signal transducer and activator of transcription 3 (STAT3) transcription factor has been previously implicated as a constitutively active oncogene in TNBC. However, its direct regulatory gene targets and tumorigenic properties have not been well characterized. By integrating RNA-seq and ChIP-seq data from 2 TNBC tumors and 4 cell lines, we discovered novel gene signatures directly regulated by STAT3 that were enriched for processes involving inflammation, immunity, and invasion in TNBC. Functional analysis revealed that STAT3 has a key role regulating invasion and metastasis, a characteristic often associated with TNBC. Our findings suggest therapies targeting STAT3 may be important for preventing TNBC metastasis.

2017-06-10 | GSE85579 | GEO

Microarray-based gene expression data from BPLER tumor explants.

Project description:The gene expression of 6 different mouse xenografts initiated by BPLER cells analyzed by microarray. Basal-like triple negative breast cancers (TNBC) have poor prognosis. To study the basal-like transcriptional profile of tumors transformed by defined genetic elements, the human breast epithelial cell line BPLER was injected into NOD/SCID mice. The resulting tumors were excised for expression analysis. Keywords: breast cancer, BPLER, metastasis, tumor stem cells, tumor initiating cells, breast adenocarcinoma BPLER cells were derived from human primary breast epithelial cells propagated in WIT medium (Ince et al, Cancer Cell, 2007). These cells were transformed with hTERT, SV40 early region and hRASV12 by retroviral transduction. BPLER have a TNBC-like phenotype in vitro and are highly enriched for tumor-initiating cells. To define the phenotype of BPLER-derived tumors in vivo, BPLER cells were injected in the mammary fat-pad of 6 NOD/SCID mice. Once tumors were palpable, mice were sacrificed and tumors excised. Total RNA was extracted using Trizol. The gene expression profile of each tumor was assessed by mRNA microarray analysis. Based on histology and principal component analysis of microarray data, BPLER tumors were remarkably similar to human primary TNBC encountered in the clinic (Petrocca et al, Cancer Cell, 2013).

2013-07-02 | E-GEOD-48444 | biostudies-arrayexpress

Gene expression profiles of triple-negative breast cancer cells under the condition of 3D proliferation

2012-05-01 | GSE36953 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data