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MMP14 empowers tumor-initiating breast cancer cells under hypoxic nutrient-depleted conditions

ABSTRACT: MMP14 empowers tumor-initiating breast cancer cells under hypoxic nutrient-depleted conditions

PROVIDER: PRJNA454197 | ENA |

REPOSITORIES: ENA

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MMP14 empowers tumor-initiating breast cancer cells under hypoxic nutrient-depleted conditions

Project description:Tumor-initiating cells (TICs) exist in breast cancer and are thought to be the cause of tumor initiation, progression, and relapse. In these processes, proteases play an important role. Additionally, conditions of the tumor milieu, including hypoxic nutrient-deprived as well as normoxic nutrient-rich environments, influence the tumor-promoting actions of neoplastic cells. Therefore, we investigated the role of proteases in TICs and their response to different environments by means of a generated immortalized TIC line. After assessing immortalized TIC tumorigenicity by limiting dilution assays in vivo and their characteristics in different environmental conditions, a transcriptome analysis was performed of iTICS cultured in hypoxic stem cell conditions and 1-7 days in normoxic standard condtitions. A high proteolytic signature was identified and further investigated by inhibitor treatment and shRNA mediated RNA interference of Mmp14.

2018-11-27 | GSE113826 | GEO

Expression array of stromal Mmp14-targeted mammary glands

Project description:Mammary gland branching morphogenesis is thought to depend on the mobilization of proteolytic machinery from the matrix metalloproteinase (MMP) family, namely MT1-MMP/MMP14, to drive coordinated epithelial cell invasion through the interstitial extracellular matrix, but the dominant effector has remained undefined. Unexpectedly, we find MMP14 controls postnatal mammary gland branching from the periductal stroma. Transcriptome profiling of stromal cell-targeted mammary glands was used to characterize the impact of stromal Mmp14-targeting on the growth factor and signaling cascades implicated in mammary gland morphogenesis. Transcriptome profiling of ductal networks and associated stroma was used to investigate the functional roles of MMP14 in the postnatal mammary gland stroma in an unbiased fashion.

2019-03-01 | GSE79088 | GEO

MMP14 knockdown at U87 brain tumor cells.Analyse of the genes responsible for cell division

Project description:Compared to the Scramble U87 cells, MMP14 ablation induces G2M arrest SABioscience Cell cycle platform, human genes. U87 cells were infected separately with eithr lentivirus carry on Scramble or sh RNA against human MMP14 gene.Equla amount of mRNA was isolated prior RT-PCR analyses

2013-03-19 | E-GEOD-45294 | biostudies-arrayexpress

Identification of differentially expressed miRNAs in hypoxic tumor-initiating cell (TIC) cultures

Project description:Identification of differentially expressed miRNAs in hypoxic tumor-initiating cell (TIC) cultures

| PRJNA493054 | ENA

Mmp14 is essential for circadian clock rhythmicity in fibroblasts

Project description:Membrane type I-matrix metalloproteinase (MT1-MMP/Mmp14) is an unusual MMP because it is essential for survival in mice with multiple organ systems being affected for reasons that are unclear. Here, we show that the protein (MT1-MMP) and gene (Mmp14) are under strict circadian clock control and conditional knockout in fibroblasts leads to ~16% of the proteome losing or inverting circadian rhythmicity. The result is loss of the actin cytoskeleton and cell-matrix adhesions and major imbalance of the matrisome. Lack of collagen-I monomer turnover results in excess fibril formation in the absence of Mmp14. In the absence of Mmp14, paired-like homeodomain transcription factor 2 (Pitx2) is upregulated and remains in the nucleus where it drives Plod2 expression. The overall result is accumulation of collagen fibrils and elevated pyridinoline crosslinking that renders collagen fibrils insoluble. In conclusion, Mmp14 is a master regulator of circadian rhythms affecting the actin cytoskeleton and cell microenvironment.

2023-10-31 | PXD031692 | Pride

Mmp14-Dependent Remodeling of the Pericellular-Dermal Collagen Interface Governs Fibroblast Survival

Project description:Dermal fibroblasts deposit type I collagen, the dominant extracellular matrix molecule found in skin, during early postnatal development. Coincident with this biosynthetic program, fibroblasts proteolytically remodel pericellular collagen fibrils by mobilizing the membrane-anchored matrix metalloproteinase, Mmp14. Unexpectedly, dermal fibroblasts in Mmp14-/- mice commit to a large-scale apoptotic program that leaves skin tissues replete with dying cells. A requirement for Mmp14 in dermal fibroblast survival is recapitulated in vitro when cells are embedded within, but not cultured atop, 3-dimensional hydrogels of cross-linked type I collagen. In the absence of Mmp14-dependent pericellular proteolysis, dermal fibroblasts fail to trigger β1 integrin activation and instead actuate a TGF-β1/phospho-JNK stress response that leads to apoptotic cell death in vitro as well as in vivo. Taken together, these studies identify Mmp14 as a requisite cell survival factor that maintains dermal fibroblast viability in postnatal dermal tissues.

2024-05-24 | GSE266914 | GEO

MMP14-wild type (WT) vs. MMP14-deficient (KO) liver mesenchymal cells derived from embryonic day (E) 16.5 mouse livers

Project description:Transcriptional profiling of systemic MMP14-KO and littermate WT mesenchymal cells in E16.5 livers. CD45-Ter119-p75NTR (NFGR)-positive liver mesenchymal cells were purified using fluorescence-activated cell sorter (FACS).

2020-01-05 | GSE139517 | GEO

Single-cell sequencing analysis reveals the tissue architecture and empowers clinical trial in advanced conjunctival melanoma

Project description:Single-cell sequencing analysis empowers clinical decision

2024-06-18 | GSE217707 | GEO

MMP14 cleaves PTH1R in the chondrocyte derived osteoblast lineage, curbing signaling intensity for proper bone anabolism

Project description:Bone homeostasis is regulated by hormones such as parathyroid hormone (PTH). While PTH can stimulate osteo-progenitor expansion and bone synthesis, how the PTH-signaling intensity in progenitors is controlled is unclear. Endochondral bone osteoblasts arise from perichondrium-derived osteoprogenitors and hypertrophic chondrocytes (HC). We found, via single-cell transcriptomics, HC descendent cells activate membrane-type 1 metalloproteinase 14 (MMP14) and the PTH pathway as they transition to osteoblasts in neonatal and adult mice. Unlike Mmp14 global knockouts, postnatal day 10 (p10) HC lineage-specific Mmp14 null mutants (Mmp14ΔHC) produce more bone. Mechanistically, MMP14 cleaves the extracellular domain of PTH1R, dampening PTH signaling, and consistent with the implied regulatory role, in Mmp14ΔHC mutants, PTH signaling is enhanced. We found HC-derived osteoblasts contribute ~50% of osteogenesis promoted by treatment with PTH 1-34 and this response was amplified in Mmp14ΔHC. MMP14 control of PTH signaling likely applies also to both HC- and non-HC-derived osteoblasts because their transcriptomes are highly similar. Our study identifies a novel paradigm of MMP14 activity-mediated modulation of PTH signaling in the osteoblast lineage, contributing new insights into bone metabolism with therapeutic significance for bone-wasting diseases.

2023-03-13 | GSE222203 | GEO

Expression array of carcinoma cell Mmp14-targeted MMTV-PyMT mammary tumors

Project description:Breast carcinoma cell invasion is thought to depend on the mobilization of the membrane-anchored matrix metalloproteinase, Mmp14/MT1-MMP, to drive the remodeling of extracellular matrix and trigger associated signaling cascades. However, the roles that this proteinase plays during breast tumor progression and invasion in vivo remain undefined. A highly penetrant syngeneic mouse model for luminal B breast cancer driven by the polyoma middle T (PyMT) antigen, in tandem with recently developed Mmp14-floxed mice and MMTV-Cre transgenics that express Cre recombinase throughout the mammary epithelial cell compartment, were used to characterize the impact of conditional Mmp14-targeting on breast carcinoma cell invasion programs in vivo. Transcriptome profiling of intact MMTV-PyMT carcinoma tumors was used to investigate the functional roles of carcinoma cell-derived MT1-MMP in MMTV-PyMT tumor progression and invasion in an unbiased fashion

2018-12-01 | GSE118466 | GEO

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