Characterization of TRKA signaling in acute myeloid leukemia.

Tropomyosin-related kinase A (TRKA) translocations have oncogenic potential and have been found in rare cases of solid tumors. Accumulating evidence indicates that TRKA and its ligand, nerve growth factor (NGF), may play a role in normal hematopoiesis and may be deregulated in leukemogenesis. Here, we report a comprehensive evaluation of TRKA signaling in normal and leukemic cells.

Targeting P-selectin blocks neuroblastoma growth.

Selectins and their ligands have been implicated in tumor growth and progression in carcinomas, but their role in neuroblastoma has not been systematically examined. In the current study we evaluated L-, P- and E-selectin binding to neuroblastoma cells and the expression of some of their known ligands, namely CD44, CD24 and P-selectin glycoprotein ligand-1 (PSGL-1). Genetic loss of PSGL-1 or CD24 and pharmacological inhibition of P-selectin reduced P-selectin binding to neuroblastoma cells i.

Notch activation inhibits AML growth and survival: a potential therapeutic approach.

Although aberrant Notch activation contributes to leukemogenesis in T cells, its role in acute myelogenous leukemia (AML) remains unclear. Here, we report that human AML samples have robust expression of Notch receptors; however, Notch receptor activation and expression of downstream Notch targets are remarkably low, suggesting that Notch is present but not constitutively activated in human AML. The functional role of these Notch receptors in AML is not known.

Notch pathway activation induces neuroblastoma tumor cell growth arrest.

Background: Notch pathway signaling has critical roles in differentiation, proliferation, and survival, and has oncogenic or tumor suppressor effects in a variety of malignancies. The goal of this study was to evaluate the effects of Notch activation on human neuroblastoma cells.

Procedure: Quantitative RT-PCR, immunoblots, and immunohistochemistry were used to determine the expression of Notch receptors (Notch1-4), cleaved Notch1 (ICN1), and downstream targets (HES1-5) in human neuroblastoma cell lines and patient tumor samples.

The bantam microRNA is a target of the hippo tumor-suppressor pathway.

Background: The Hippo tumor-suppressor pathway has emerged as a key signaling pathway that controls tissue size in Drosophila. Hippo signaling restricts tissue size by promoting apoptosis and cell-cycle arrest, and animals carrying clones of cells mutant for hippo develop severely overgrown adult structures. The Hippo pathway is thought to exert its effects by modulating gene expression through the phosphorylation of the transcriptional coactivator Yorkie.

The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis.

Merlin, the protein product of the Neurofibromatosis type-2 gene, acts as a tumour suppressor in mice and humans. Merlin is an adaptor protein with a FERM domain and it is thought to transduce a growth-regulatory signal. However, the pathway through which Merlin acts as a tumour suppressor is poorly understood.

Senseless acts as a binary switch during sensory organ precursor selection.

During sensory organ precursor (SOP) specification, a single cell is selected from a proneural cluster of cells. Here, we present evidence that Senseless (Sens), a zinc-finger transcription factor, plays an important role in this process. We show that Sens is directly activated by proneural proteins in the presumptive SOPs and a few cells surrounding the SOP in most tissues.

Hippo promotes proliferation arrest and apoptosis in the Salvador/Warts pathway.

Proliferation and apoptosis must be precisely regulated to form organs with appropriate cell numbers and to avoid tumour growth. Here we show that Hippo (Hpo), the Drosophila homologue of the mammalian Ste20-like kinases, MST1/2, promotes proper termination of cell proliferation and stimulates apoptosis during development. hpo mutant tissues are larger than normal because mutant cells continue to proliferate beyond normal tissue size and are resistant to apoptotic stimuli that usually eliminate extra cells.

Shar-pei mediates cell proliferation arrest during imaginal disc growth in Drosophila.

During animal development, organ size is determined primarily by the amount of cell proliferation, which must be tightly regulated to ensure the generation of properly proportioned organs. However, little is known about the molecular pathways that direct cells to stop proliferating when an organ has attained its proper size. We have identified mutations in a novel gene, shar-pei, that is required for proper termination of cell proliferation during Drosophila imaginal disc development.