June 2008 Molecular Cancer Research Highlights

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Selected Articles from the June 1, 2008 Issue

The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Molecular Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the June 2008 issue of Molecular Cancer Research

CD133(+) Induction of Medulloblastoma Neurospheres

The neural precursor surface marker CD133 is enriched in brain cancer stem cells (CSC), and its gene expression is significantly higher in the radioresistant and recurrent brain tumor tissue. In this study, Annabi and colleagues demonstrate that intracerebral implantation of brain cancer cells triggers the expression of CD133(+) brain tumor-derived CSC during tumor development. Increased expression of MMP-9 and MT1-MMP, two matrix metalloproteinases which respectively contribute to blood-brain barrier opening and to the radioresistance phenotype of brain tumor cells, was correlated with in vitro neurosphere formation. Targeting MMP-9 and/or MT1-MMP may constitute promising new anticancer therapies in destroying brain tumor-initiating stem cells. 

IR-Induced EGFR Activation via Nitric Oxide

SFRP4 Inhibits Wnt7a Signaling

Carmon and Loose demonstrate that Wnt7a can activate two distinct Wnt signaling pathways in endometrial cells depending on the context of Fzd receptors that are present. SFRP4, which is highly expressed by stomal cells of the endometrium, was able to block signaling by both pathways. SFRP4 was shown to directly bind Wnt7a to inhibit function and to suppress endometrial cancer cell growth. These data suggest that loss of SFRP4 expression by both genetic and epigenetic mechanisms can lead to excessive Wnt signaling, overactive β-catenin, and increased proliferation that may ultimately contribute to the onset of endometrial cancer.  

PSA-like kallikreins (hK2 and hK4) and their potential targets, protease-activated receptors (PAR), are elevated in prostate cancer, but their interaction in cancer progression is unknown. To test their roles, recombinant hK2 and hK4 were used by Mize and colleagues and shown to stimulate ERK1/2 signaling in DU145, PC-3, and LNCaP cells. These kallikreins also stimulate the proliferation of the DU145 cells. It was found that hK4 specifically activates both PAR1 and PAR2 while hK2 activates only PAR1. These data suggest that hK2 and hK4 may directly stimulate prostate cancer cell proliferation and may be potentially important targets for future drug therapy.