TFPI inhibits breast cancer progression by suppressing ERK/p38 MAPK signaling pathway.

Background: Tissue factor pathway inhibitor-1 (TFPI) is a serine protease inhibitor, which is responsible for inactivating TF-induced coagulation. Recently, increasing studies revealed that TFPI was lowly expressed in tumor cells and exhibited the antitumor activity.

Objective: The aim of this study was to explore the role and underlying molecular mechanisms of TFPI in breast cancer.

Regulation of lymphocyte development by cell-type-specific interpretation of Notch signals.

Notch signaling pathways exert diverse biological effects depending on the cellular context where Notch receptors are activated. How Notch signaling is integrated with environmental cues is a central issue. Here, we show that Notch activation accelerates ubiquitin-mediated and mitogen-activated protein kinase (MAPK)-dependent degradation of E2A transcription factors and Janus kinases, molecules essential for both B- and T-lymphocyte development.

Cell cycle quiescence of early lymphoid progenitors in adult bone marrow.

Lymphocyte production in bone marrow (BM) requires substantial cell division, but the relationship between largely quiescent stem cells and dividing lymphoid progenitors is poorly understood. Therefore, the proliferation and cell cycle status of murine hematopoietic progenitors that have just initiated the lymphoid differentiation program represented the focus of this study. Continuous bromo-2'-deoxyuridine (BrdU) incorporation and DNA/RNA analysis by flow cytometry revealed that a surprisingly large fraction of RAG-1(+)c-kit(hi) early lymphoid progenitors (ELPs) and RAG-1(+)c-kit(lo) pro-lymphocytes (Pro-Ls) in adult BM were in cell cycle quiescence.

Tracing the first waves of lymphopoiesis in mice.

RAG1/GFP knock-in mice were used to precisely chart the emergence and expansion of cells that give rise to the immune system. Lymphopoietic cells detectable in stromal co-cultures arose as early as E8.5, i.

Propensity of adult lymphoid progenitors to progress to DN2/3 stage thymocytes with Notch receptor ligation.

Notch family receptors control critical events in the production and replenishment of specialized cells in the immune system. However, it is unclear whether Notch signaling regulates abrupt binary lineage choices in homogeneous progenitors or has more gradual influence over multiple aspects of the process. A recently developed coculture system with Delta 1-transduced stromal cells is being extensively used to address such fundamental questions.

Lymphoid progenitors and primary routes to becoming cells of the immune system.

Extraordinary progress has been made in charting the maturation of hematopoietic cells. However, these charted processes do not necessarily represent obligate pathways to specialized types of lymphocytes. In fact, there is a degree of plasticity associated with primitive progenitors.

Derivation of 2 categories of plasmacytoid dendritic cells in murine bone marrow.

Plasmacytoid dendritic cells (pDCs) competent to make type I interferon were rigorously defined as a Ly-6C(+) and CD11c(Lo) subset of the B220(+)CD19(-) CD43(+)CD24(Lo) bone marrow (BM) Fraction A. Otherwise similar Ly6C(-) cells expressed the natural killer (NK) markers DX5 and NK1.1.