Tis11 mediated mRNA decay promotes the reacquisition of Drosophila intestinal stem cell quiescence.

Adult stem cell proliferation rates are precisely regulated to maintain long-term tissue homeostasis. Defects in the mechanisms controlling stem cell proliferation result in impaired regeneration and hyperproliferative diseases. Many stem cell populations increase proliferation in response to tissue damage and reacquire basal proliferation rates after tissue repair is completed.

PGE(2) is a UVR-inducible autocrine factor for human melanocytes that stimulates tyrosinase activation.

Prostaglandins activate signalling pathways involved in growth, differentiation and apoptosis. Prostaglandin E(2) (PGE(2)) is released by keratinocytes following ultraviolet irradiation (UVR) and stimulates the formation of dendrites in melanocytes. We show that multiple irradiations of human melanocytes with UVR-activated cPLA(2), the rate-limiting enzyme in eicosanoid synthesis and stimulated PGE(2) secretion.

Plexin B1 suppresses c-Met in melanoma: a role for plexin B1 as a tumor-suppressor protein through regulation of c-Met.

Melanoma arises through complex genetic and epigenetic changes, resulting in uncontrolled proliferation, invasion, and metastatic disease. Semaphorins regulate axon guidance through interaction with their receptors, plexins and neuropilins. Plexin B1, the semaphorin 4D receptor, activates oncogenic receptors c-Met and ErbB-2 in several cell types, suggesting it promotes tumor growth through stimulation of these receptors.

Plexin C1, a receptor for semaphorin 7a, inactivates cofilin and is a potential tumor suppressor for melanoma progression.

Melanocytes are progenitor cells for melanoma, which arises through step-wise progression from dysplastic to invasive, to metastatic tumor. Our previous data showed that semaphorin 7A (Sema7A), a protein involved in axon guidance, stimulates melanocyte adhesion and dendricity through opposing actions of beta1-integrin and Plexin C1 receptors. We now show that Plexin C1 is diminished or absent in human melanoma cell lines; analysis of tissue microarrays of nevi, melanoma, and metastatic melanoma showed a decrease in Plexin C1 expression in metastatic melanoma, and an inverse correlation of Plexin C1 expression with depth of invasion.

Prostaglandin E2 regulates melanocyte dendrite formation through activation of PKCzeta.

Prostaglandins are lipid signaling intermediates released by keratinocytes in response to ultraviolet irradiation (UVR) in the skin. The main prostaglandin released following UVR is PGE(2), a ligand for 4 related G-protein-coupled receptors (EP(1), EP(2), EP(3) and EP(4)). Our previous work established that PGE(2) stimulates melanocyte dendrite formation through activation of the EP(1) and EP(3) receptors.

Semaphorin 7a promotes spreading and dendricity in human melanocytes through beta1-integrins.

Described as secreted and membrane-bound proteins important for neural pathfinding, the class of proteins called Semaphorins are expressed in multiple tissue types and are involved in diverse biologic processes. In this study, we describe the function of Semaphorin 7a, a membrane-bound Semaphorin known to stimulate neurite outgrowth, on human melanocytes. We show that Semaphorin 7a is expressed by human keratinocytes and fibroblasts in vitro and in vivo and that melanocytes express Plexin C1, a receptor for Semaphorin 7a.