Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Laminin-binding integrins are essential for the maintenance of functional secretory epithelium in lactation

ABSTRACT: Integrin dimers α3/β1, α6/β1 and α6/β4 are the mammary epithelial cell receptors for laminins, which are major components of the basement membrane, a specialized extracellular matrix surrounding the mammary epithelium. The roles of specific basement membrane components and their integrin receptors in the regulation of functional gland development have not been analyzed in detail. To investigate the functions of laminin-binding integrins, we obtained mutant mice with mammary luminal cell-specific deficiencies of the α3 and α6 integrin chains generated by the Cre-Lox approach. During pregnancy, mutant mice displayed low levels of luminal progenitor activity and retarded lobulo-alveolar development, whereas their mammary glands seemed to be functional at the onset of lactation. Myoepithelial cell morphology was markedly altered in mutant glands, suggesting cellular compensation mechanisms involving cytoskeleton reorganization. However, lactation was not sustained in mutant mice, and the glands underwent precocious involution. Inactivation of the p53 gene rescued the growth defects but did not restore lactogenesis in mutant mice. This study reveals an essential role for laminin-binding integrins in functional mammary gland development.

ORGANISM(S): Mus musculus

PROVIDER: GSE132281 | GEO | 2020/02/04

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Laminin-binding integrins are essential for the maintenance of functional secretory epithelium in lactation [luminal cells]

Project description:Integrin dimers α3/β1, α6/β1 and α6/β4 are the mammary epithelial cell receptors for laminins, which are major components of the basement membrane, a specialized extracellular matrix surrounding the mammary epithelium. The roles of specific basement membrane components and their integrin receptors in the regulation of functional gland development have not been analyzed in detail. To investigate the functions of laminin-binding integrins, we obtained mutant mice with mammary luminal cell-specific deficiencies of the α3 and α6 integrin chains generated by the Cre-Lox approach. During pregnancy, mutant mice displayed low levels of luminal progenitor activity and retarded lobulo-alveolar development, whereas their mammary glands seemed to be functional at the onset of lactation. Myoepithelial cell morphology was markedly altered in mutant glands, suggesting cellular compensation mechanisms involving cytoskeleton reorganization. However, lactation was not sustained in mutant mice, and the glands underwent precocious involution. Inactivation of the p53 gene rescued the growth defects but did not restore lactogenesis in mutant mice. This study reveals an essential role for laminin-binding integrins in functional mammary gland development.

2020-02-04 | GSE132349 | GEO

Combination scaffolds of salmon fibrin, hyaluronic acid, and laminin for human neural stem cell tissue engineering

Project description:A goal of this project is to evaluate the integrin mRNA expression in human neural stem/progenitor cells (hNSPC) using high-throughput sequencing technologies. We found high levels of mRNA expression for the β1, α7, α3, α6, β5, αV, α5, and α9 integrins. This suggests that hNSPCs may express integrin receptors that can bind fibrinogen and laminin proteins.

2016-12-14 | GSE76011 | GEO

cDNA array of the new human breast cancer cell line EM-G3 derived from breast cancer progenitor cells

Project description:Analysis of gene expression with cDNA array showed high expression levels of apoptosis activator Apaf1, membrane proteins CD44 and TGFR1β, integrin family members α2, α3, α6, αV and β1, p53 regulator MDM2, p21Ras GTP-ase activating molecule RasA1, and extracellular matrix-associated protein thrombospondin I. Expression of EGFR confirmed the immunocytochemical results, and expression of integrin α6 and CD44 support basal epithelial character of the EM-G3 cells. Keywords: cDNA array, breast cancer cell line

2005-11-08 | GSE3570 | GEO

Deciphering the mammary stem cell niche: a role for laminin-binding integrins

Project description:Integrin dimers a3/b1, a6/b1 and a6/b4 are the receptors of mammary epithelial cells for Laminin, major component of the mammary basement membrane. Antibodies against a6 and a3 integrin chains serve to isolate stem cell enriched populations from mammary epithelium, however, role of integrin dimers comprising these chains in the control of mammary stem cell activity are not known. To investigate the role of Laminin-binding integrins in the control of mammary stem cell function, a3 and a6 chains were deleted from mammary basal cells in vitro using Cre-recombinase carrying adenovirus. We found that deletion of single integrin chain (either a3, or a6) did not significantly affect stem cell potential as evaluated by transplantation and mammosphere assays, whereas basal cells depleted of both a3 and a6 integrin chains (a3a6KO) presented severely diminished stem cell activity. In this study the transcriptional profiles of a3a6KO were analysed and compared to those of control cells.

2019-04-23 | GSE117120 | GEO

Integrin α3b1-dependent gene expression in MDA-MB-231 breast cancer cells

Project description:Gene-level and exon-level analysis of gene expression in MDA-MB-231 cells that stably express control shRNA or integrin α3-targeting shRNA. The laminin-332-binding integrin α3b1 is expressed highly in many breast cancer cells, but its roles in regulating gene expression programs that promote breast cancer progression have not been explored. In order to identify genes that are regulated by α3b1 in human breast cancer cells, we used a lentiviral approach to express an α3-targeting shRNA to suppress integrin α3b1 in MDA-MB-231 cells, and we identified subsequent changes in gene expression and alternate exon useage. We used the Affymetrix Human Exon 1.0 ST platform to analyze biological replicates of MDA-MB-231 cells that were transduced with lentivirus to stably express either control shRNA or α3-targeting shRNA. Array data was processed by Affymetrix Exon Array Computational Tool.

2014-05-02 | E-GEOD-43097 | biostudies-arrayexpress

Epithelial HVEM maintains intraepithelial T cell survival and contributes to host protection

Project description:Intraepithelial T cells (IET) provide surveillance of the intestinal epithelium, but little is known about how epithelial-derived signals regulate IET. Analyzing mice with a deficiency for the herpes virus entry mediator (HVEM), a member of the TNF receptor superfamily (TNFRSF14), we showed HVEM maintains the survival of subsets of small intestine IET through interactions with TNFSF14 (LIGHT). RNA-seq and analysis of organoids showed that epithelial cell expressed HVEM provided signals that were required for optimal synthesis of collagen IV. Collagen IV supported IET survival in vitro via interactions with IET β1 integrins. Furthermore, absence of β1 integrin expression in T lymphocytes decreased TCR αβ+ IET in vivo. Intravital microscopy showed that the patrolling movement of all IET was reduced without epithelial HVEM, and we hypothesize that collagen IV interactions with β1 integrins could have been responsible. As likely consequences of decreased total IET number and movement, protective responses to Salmonella enterica were reduced in mice lacking either epithelial HVEM, HVEM binding partners CD160 or LIGHT, or β1 integrins. Therefore, these data defined a circuit whereby epithelial HVEM regulated IET indirectly, through basement membrane synthesis that interacts with T cell integrins, with consequences for mucosal immunity.

2022-06-17 | GSE206183 | GEO

Integrin α3b1-dependent gene expression in MDA-MB-231 breast cancer cells

2014-05-02 | GSE43097 | GEO

Absence of integrin α3 modulates the integrin landscape of human keratinocytes

Project description:Integrins are among the most abundant cell surface receptors constituting the principal adhesion receptors for the extracellular matrix (ECM), providing a physical anchor for the cell and triggering multiple intracellular signalling events. Loss-of function mutations of the integrin α3 gene (ITGA3) have been recently disclosed in patients with interstitial lung disease, congenital nephrotic syndrome and junctional epidermolysis bullosa, a multiorgan disorder with fatal outcome. In these patients, the respiratory function is strongly impaired and the kidneys are variably affected, whereas skin fragility is rather mild, has a delayed onset after birth or remains unrecognized, suggesting that integrin α3 differently influences the development and homeostasis of these organs. Here we employed authentic human keratinocytes bearing a naturally occurring integrin α3 loss-of-function mutation as a prototype to characterize the molecular mechanisms launched by the constitutional absence of this integrin subunit. To validate our findings, we generated new cellular models, including an additional ILNEB patient cell line, ITGA3 rescued and knockdown cells. We show that keratinocytes lacking a functional α3 subunit have an activated cellular phenotype with a switch in the pattern of integrin α subunits on the cell surface. These assure spreading and adhesion of epidermal keratinocytes but also drive the migratory phenotype of these cells.

2017-03-16 | GSE75838 | GEO

Effect of laminin adhesion on basal human mammary epithelial cells

Project description:Mammary epithelium is composed by luminal and basal epithelial cells, which are adhere to the basement membrane (BM). To dissect how basal cell functions are regulated by BM laminin adhesion, we performed RNA sequencing of basal human mammary epithelial cells adhered on laminin-111, -421 or -521 coated cell culture plates for 48 hours.

2022-11-07 | GSE197950 | GEO

TMTC1 promotes invasiveness of ovarian cancer

Project description:Ovarian cancer is the most lethal gynecological malignancy and is characterized by peritoneal disseminated metastasis. Although O-mannosyltransferase TMTC1 is highly expressed by ovarian cancer, its pathophysiologic role in ovarian cancer remains unclear. Here, immunohistochemistry showed that TMTC1 was overexpressed in ovarian cancer tissues compared with the adjacent non-tumor ovarian tissues and high TMTC1 expression was associated with poor prognosis in patients with ovarian cancer. Silencing TMTC1 reduced ovarian cancer cell viability, migration, and invasion in vitro as well as suppressed peritoneal tumor growth and metastasis in vivo. Moreover, TMTC1 knockdown reduced cell-laminin adhesion, which was associated with the decreased phosphorylation of FAK at pY397. Conversely, TMTC1 overexpression promoted these malignant properties in ovarian cancer cells. Glycoproteomic analysis and Concanavalin A (ConA) pull-down assays showed that integrins β1 and β4 were novel O-mannosylated protein substrates of TMTC1. Furthermore, TMTC1-mediated cell migration and invasion were significantly reversed by siRNA-mediated knockdown of integrin β1 or β4. Collectively, these results suggest that TMTC1-mediated invasive behaviors are primarily through integrins β1 and β4 and that TMTC1 is a potential therapeutic target for ovarian cancer.

2023-10-24 | PXD037907 | Pride

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