The niche under siege: novel targets for metastasis therapy.

Metastasis is an inefficient process and most cancer cells fail to colonize secondary sites. There are several possible reasons for this. First, the nature of the infiltrating cells is important as a small population of cancer stem cells has been shown to have exclusive metastasis-initiating potential.

Cancer stem cells: never Wnt away from the niche.

Purpose Of Review: The last years of cancer research have established the concept of cancer stem cells (CSCs) as a subpopulation of cells within a tumor entirely responsible for tumorigenesis. This has aroused expectations that targeting cancer stem cells would allow effective tumor eradication. This review aims to summarize the relevant achievements in the field and to highlight the complex mechanisms that are involved in regulating CSC function.

Chk1 instability is coupled to mitotic cell death of p53-deficient cells in response to virus-induced DNA damage signaling.

Adeno-associated virus (AAV) DNA, by mimicking a stalled replication fork, provokes a DNA damage response that can arrest cells in the G2/M phase of the cell-cycle. This response depends strictly on DNA damage signaling kinases ATR and Chk1. Here, we used AAV to study long-term effects of DNA damage signaling in cells with altered p53 status.

The tyrosinase enhancer is activated by Sox10 and Mitf in mouse melanocytes.

The terminal differentiation of melanocytes is associated with the transcriptional activation of genes responsible for pigment production such as tyrosinase. Pigment cell-specific transcription factors, such as Mitf, as well as specific proximal and distal regulatory elements (DRE) are implicated in the tight control of tyrosinase expression during development and adulthood. Proper tyrosinase expression in melanocytes depends upon the presence of a DRE that is located at -15 kb and provides enhancer activity via a central element termed core-enhancer.

Alveolar and lactogenic differentiation.

The mouse mammary gland is a complex tissue that proliferates and differentiates under the control of systemic hormones during puberty, pregnancy and lactation. Once a highly branched milk duct system has been established, during mid/late pregnancy, alveoli, little saccular outpouchings, sprout all over the ductal system and differentiate to become the sites of milk secretion. Here, we review the emerging network of the signaling pathways that connects hormonal stimuli with locally produced signaling molecules and the components of intracellular pathways that regulate alveologenesis and lactation.

A conserved transcriptional enhancer that specifies Tyrp1 expression to melanocytes.

Pigment cells of mammals originate from two different lineages: melanocytes arise from the neural crest, whereas cells of the retinal pigment epithelium (RPE) originate from the optic cup of the developing forebrain. Previous studies have suggested that pigmentation genes are controlled by different regulatory networks in melanocytes and RPE. The promoter of the tyrosinase-related family gene Tyrp1 has been shown to drive detectable transgene expression only to the RPE, even though the gene is also expressed in melanocytes as evident from Tyrp1-mutant mice.

The fibroblast growth factor-2 is not essential for melanoma formation in a transgenic mouse model.

Fibroblast growth factor 2 (FGF2) has been assigned a role in melanocyte proliferation and in development of human cutaneous melanoma. We have used a transgenic mouse melanoma model in combination with mice lacking mouse FGF2 to analyse the possible implication of FGF2 in melanomagenesis. Tyr::N-rasQ61K transgenic mice which are deficient for FGF2 and the tumor suppressors p16INK4a and p19ARF are hyperpigmented and develop cutaneous metastasizing melanoma, with no difference to mice wildtype for FGF2.

Integrin-mediated adhesion and soluble ligand binding stabilize COX-2 protein levels in endothelial cells by inducing expression and preventing degradation.

Cyclooxygenase-2 (COX-2), a key enzyme in prostaglandin synthesis, is highly expressed during inflammation and cellular transformation and promotes tumor progression and angiogenesis. We have previously demonstrated that endothelial cell COX-2 is required for integrin alphaVbeta3-dependent activation of Rac-1 and Cdc-42 and for endothelial cell spreading, migration, and angiogenesis (Dormond, O., Foletti, A.

The Tyr (albino) locus of the laboratory mouse.

The albino mouse was already known in ancient times and was apparently selectively bred in Egypt, China, and Japan. Thus, it is not surprising that the c or albino locus (now the Tyr locus) was among the first used to demonstrate Mendelian inheritance in mammals at the dawn of the past century. This locus is now known to encode tyrosinase, the rate-limiting enzyme in the production of melanin pigment, and the molecular basis of the albino ( Tyr(c)) mutation is known.

Notch1 can contribute to viral-induced transformation of primary human keratinocytes.

The human papillomavirus (HPV) is the most significant causative agent in the development of cervical cancer. Despite its presence in almost all cervical cancers, HPV by itself is unable to transform a normal cell to a cancerous one. Instead, additional cellular mutations are required to supplement the HPV oncoproteins E6 and E7.