July 2008 Molecular Cancer Research Highlights

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Selected Articles from the July 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 July 2008 issue of Molecular Cancer Research

Fibroblasts Mediate Tobacco-Induced Cell Aggressiveness

Although some aspects of tobacco-induced tumorigenesis are well established, the potential importance of epithelial-stromal interactions in this process remains largely unknown. Here, Coppe and colleagues present evidence that tobacco alters the secretory phenotype of fibroblasts, enabling them to increase proliferation and invasion of epithelial cells. These findings add a new and potentially important dimension—non-mutagenic activation of stromal pathways—to our understanding of how noxious environmental agents might promote cancer.

ALDH, CD133, and Liver Cancer Stem Cells

The Role of Pak4 in Cancer

Studied for over 15 years the exact mode of action of the WT1 Wilms tumor suppressor protein remains to be fully elucidated. A previous microarray analysis identified that WT1 up-regulated MKP3 upon WT1A induction in Saos-2 cells. In this issue, Morrison and colleagues validated the array data and identified MKP3 as a direct WT1 target by transient reporter assays and chromatin immunoprecipitation. In addition they showed that induction of WT1 in SAOS and other cells dramatically decreased phosphorylated ERK1/2 levels, indicating that WT1 is a negative regulator of the MAP kinase pathway. WT1 was previously shown to inhibit transformation by the Ras oncogene in a focus forming assay. Depletion of MKP3 by shRNA significantly disabled the ability of WT1 to suppress foci formation by ras. With validation of MKP3 and the prior identification of Spry1, another inhibitor of MAP kinase activation as a WT1 target gene, it appears that one mode of tumor suppression by WT1 is by suppression of signaling through the MAP kinase pathway.