Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptome analysis of Scramble control and CDK14-sh MDA-MB-231 cells

ABSTRACT: Wnt/β-catenin signaling pathway has become a key signaling pathway regulating mammary organogenesis and oncogenesis. However, the therapeutic methods by targeting Wnt pathway against breast cancer has been limited. To address this challenge, we investigated the function of cyclin-dependent kinase 14 (CDK14), a member of Wnt signaling pathway, in mammary development and breast cancer progression. We showed that CDK14 was expressed in the mammary basal layer and elevated in triple negative breast cancer (TNBC). CDK14 knockdown reduces colony formation ability and regeneration capacity of mammary basal cells, and significantly inhibits murine MMTV-Wnt-1 basal-like mammary tumor progression. Excitingly, knockdown of CDK14 or pharmacological inhibition of CDK14 by FMF-04-159-2 significantly inhibited the progression and metastasis of human TNBC. Mechanistically, CDK14 inhibition inhibits mammary regeneration and TNBC progression by attenuating Wnt/β-catenin signaling. Together, we demonstrated that CDK14 regulates mammary regeneration and breast tumorigenesis, and is a promising therapeutic target for TNBC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE197000 | GEO | 2022/02/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcriptome analysis of Scramble control and Cdk14-sh mouse mammary basal cells

Project description:Wnt/β-catenin signaling pathway has become a key signaling pathway regulating mammary organogenesis and oncogenesis. However, the therapeutic methods by targeting Wnt pathway against breast cancer has been limited. To address this challenge, we investigated the function of cyclin-dependent kinase 14 (CDK14), a member of Wnt signaling pathway, in mammary development and breast cancer progression. We showed that CDK14 was expressed in the mammary basal layer and elevated in triple negative breast cancer (TNBC). CDK14 knockdown reduces colony formation ability and regeneration capacity of mammary basal cells, and significantly inhibits murine MMTV-Wnt-1 basal-like mammary tumor progression. Excitingly, knockdown of CDK14 or pharmacological inhibition of CDK14 by FMF-04-159-2 significantly inhibited the progression and metastasis of human TNBC. Mechanistically, CDK14 inhibition inhibits mammary regeneration and TNBC progression by attenuating Wnt/β-catenin signaling. Together, we demonstrated that CDK14 regulates mammary regeneration and breast tumorigenesis, and is a promising therapeutic target for TNBC.

2022-04-29 | GSE201526 | GEO

Transcriptome analysis of FMF-04-159-2 treated MDA-MB-231 cells

2022-02-27 | GSE197213 | GEO

A Novel Role of Wnt/β Catenin Signaling in Regulating the Nucleolus in Triple Negative Breast CancerA Novel Role of Wnt/β Catenin Signaling in Regulating the Nucleolus in Triple Negative Breast Cancer

Project description:Breast cancer is one of the most common types of cancer in women. One key signaling pathway known to regulate tumor growth, metabolic adaptation, and cellular stress response in breast cancer is Wnt signaling. Breast cancer patients, specifically triple negative breast cancer (TNBC), with upregulated Wnt signaling often have a poor clinical prognosis. However, the effects of Wnt/β-catenin signaling on the nucleolus and the resultant impact on cancer development and progression remain unclear. A notable reduction was observed in the number of nucleoli per nucleus in response to Wnt/β-catenin signaling inhibition in multiple TNBC cell lines. Our comparative proteomic analysis revealed several changes in the composition of the nucleolar proteome of TNBC cells upon inhibition of Wnt signaling. Overall, we demonstrate that Wnt/β-catenin signaling will affects nucleolar functionality and thus influences breast cancer progression. Understanding the role of Wnt signaling in the nucleolus and breast cancer is a critical step towards developing novel therapeutic options for the treatment of breast cancer.

2021-03-05 | PXD021181 | Pride

FZD7 Plays a Critical Role in Triple Negative Breast Cancer Proliferation

Project description:Breast cancer is genetically and clinically heterogeneous. Triple negative cancer (TNBC) is a subtype of breast cancer usually associated with poor outcome and lack of benefit from target therapy. A pathway analysis in a microarray study was performed using TNBC compared with non-triple negative breast cancer (non-TNBC). Overexpression of several Wnt pathway genes, such as frizzled homolog 7 (FZD7), Low density lipoprotein receptor-related protein 6 (LRP6) and transcription factor 7 (TCF7) has been observed in TNBC. Focus was given to the Wnt pathway receptor, FZD7. To validate its function, inhibition of FZD7 using FZD7shRNA was carried out. Notably decreased cell proliferation, suppressed invasiveness and colony formation in triple negative MDA-MB-231 and BT-20 cells were observed. Mechanism study indicated that these effects occurred through silencing the canonical Wnt signaling pathway, as evidenced by loss of nuclear accumulation of ï?¢-catenin and decreased transcriptional activity of TCF7. In vivo study revealed that FZD7shRNA significantly suppressed the tumor formation in xenotransplation mice due to decrease cell proliferation. Our finding suggests that FZD7 involved canonical Wnt signaling pathway is essential for tumorigenesis of TNBC. Thus, FZD7 may be a biomarker and a potential therapeutic target for triple negative breast cancer. 14 pretreatment non-triple negative breast tumors compare with 5 triple negative breast tumor.

2011-06-01 | E-GEOD-27447 | biostudies-arrayexpress

Expression data from sorted control and Pygo2-null mouse mammary stem/basal cells

Project description:Skin-mammary specific knockout (SSKO) of Pygo2 (K14-cre; Pygo2 flox/-) , a WNT signaling co-activator, results in defective mouse mammary gland development. The FACS sorted mammary stem cell (MaSC)/basal population from Pygo2 SSKO mammary gland displays biased differentiation towards luminal/alveolar lineage in vitro, and reduced regeneration rate of new mammary gland in vivo To gain the insight into gene expression profiles in control and Pygo2 SSKO mammary epithelial cells (MECs), we sorted the freshly isolated mouse MECs into MaSC/basal (Lin-CD29hiCD24+) and mature luminal population (Lin-CD29lowCD24+CD61-), and extract total RNA for cDNA microarray analysis

2013-09-05 | E-GEOD-45826 | biostudies-arrayexpress

Expression data from sorted control and Pygo2-null mouse mammary stem/basal cells

2013-09-05 | GSE45826 | GEO

SOX4 AND SMARCA4 COOPERATIVELY REGULATE PI3K SIGNALING THROUGH TRANSCRIPTIONAL ACTIVATION OF TGFBR2 IN BASAL LIKE BREAST CANCER

Project description:Dysregulation of PI3K/Akt signaling is a dominant feature in basal-like or triple-negative breast cancers (TNBC). However, the mechanisms regulating this pathway are largely unknown in this subset of aggressive tumors. Here we demonstrate that the transcription factor SOX4 is a key regulator of PI3K signaling in TNBC. Genomic and proteomic analyses coupled with mechanistic studies identified TGFBR2 as a direct transcriptional target of SOX4 and demonstrated that TGFBR2 is required to mediate SOX4-dependent PI3K signaling. We further report that SOX4 and the SWI/SNF ATPase SMARCA4, which are uniformly overexpressed in basal-like tumors, form a previously unreported complex that is required to maintain an open chromatin conformation at the TGFBR2 regulatory regions in order to mediate TGFBR2 expression and PI3K signaling. Collectively, our findings delineate the mechanism by which SOX4 and SMARCA4 cooperatively regulate PI3K/Akt signaling and suggest that this complex may play an essential role in TNBC genesis and/or progression.

2021-03-02 | PXD022811 | Pride

SOX4 AND SMARCA4 COOPERATIVELY REGULATE PI3K SIGNALING THROUGH TRANSCRIPTIONAL ACTIVATION OF TGFBR2 IN TRIPLE NEGATIVE BREAST CANCER

2021-03-03 | PXD022596 | Pride

BCL11A: A Novel Breast Cancer Gene which Plays a Critical Role in Mammary Stem Cells and Progenitors

Project description:Triple negative breast cancer (TNBC) has poor prognostic outcome compared to other types of breast cancer1. At present the molecular and cellular mechanisms underlying TNBC pathology are not well understood1. Here we report that the transcription factor BCL11A is overexpressed in TNBC including basal-like breast cancer (BLBC) and that its genomic locus is amplified in up to 38% of BLBC tumours. BCL11A overexpression in immortalised human breast epithelial cells promotes tumour formation in xenograft models, whereas knockdown of BCL11A in TNBC cell lines suppresses their tumourigenic potential. In the DMBA-induced mouse mammary tumour model, Bcl11a is found to be essential for tumourigenesis since deletion of Bcl11a before DMBA treatment substantially decreases tumour formation, even in p53-null cells, and inactivation of Bcl11a in established tumours causes their regression. At the cellular level, BCL11A overexpression enhances clonogenicity in vitro whereas its deletion in the mouse causes a reduction in the number of mammary epithelial stem and progenitor cells. Thus, BCL11A has an important role in the genesis of TNBC and in normal mammary epithelial cells. This study highlights the importance of further investigation of BCL11A in breast cancer diagnosis and targeted therapies. [Mouse] KO is bcl11a deleted mammary stem cells. WT are mammary stem cells with intact Bcl11a. [Human] HMLE tumors overexpressing BCL11A.

2014-11-18 | E-GEOD-63386 | biostudies-arrayexpress

Targeted CRISPR interference and activation of microRNA-3662-HBP1 axis controls tumor progression of triple-negative breast cancer

Project description:MicroRNA-3662 (miR-3662) is not or very low expressed in normal human tissues but highly expressed in almost all types of human cancers, including breast cancer. However, the functional role of miR-3662 in human cancers remains a topic of debate. First, our bioinformatic analysis in the Cancer Genome Atlas dataset showed that miR-3662 expression is higher in triple-negative breast cancer (TNBC) and African American breast cancer than in other types of breast cancer. Next, we found that inhibition or knockout of endogenous mature miR-3662 in human TNBC cells suppresses cell proliferation and migration in vitro and tumor growth and metastasis in vivo. Functional analysis revealed that knockout of miR-3662 reduces the activation of Wnt/β-catenin signaling in TNBC cells. Finally, using dual-luciferase assay, miRNA/mRNA immunoprecipitation assay, and CRISPR-mediated miR-3662 activation and repression, we further identified that HMG-box transcription factor 1 (HBP-1), a Wnt/β-catenin signaling inhibitor, is a direct target of miR-3662 and is most likely responsible for miR-3662-mediated TNBC cell proliferation. Our results suggest that miR-3662 plays an oncogenic role in tumor progression and metastasis via a miR-3662-HBP1 axis, which negatively regulates Wnt /β-catenin signaling pathway in TNBC cells.

2022-01-26 | GSE169128 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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