March 2008 Molecular Cancer Research Highlights

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

Autotaxin-VEGF Positive Feedback Loop

ADAM-15 in Breast Cancer

The disintegrin-metalloproteinase ADAM-15 is a transmembrane protease with potential roles in cell adhesion, proteolysis, and signaling. Human breast cancers express multiple alternatively spliced forms that differ in the cytoplasmic domains that they encode, with two variants (ADAM-15A and -15B) being associated with worse survival in node-negative cancer patients. Another isoform ADAM-15C was linked with improved survival in node-positive patients. Overexpression in cancer cell lines led to isoform-specific effects on cell adhesion, migration, invasion, and metastasis. The three variant cytoplasmic domains associate with overlapping sets of intracellular signaling effectors, which may underlie their relationships with tumor aggressiveness. 

Rb Binding and Permanent Repression

Sprouty (Spry) proteins regulate receptor tyrosine kinase signaling pathways. By inducibly expressing Spry4 in pancreatic β cells, Jäggi and colleagues investigated its functional role in islet of Langerhans development and in a β–cell carcinogenesis mouse model. Spry4 expression in normal β cells resulted in smaller islets, more β cells per islet, and disrupted islet cell architecture. These effects were likely due to impaired cell adhesion and migration, as shown by Spry4 expression in cultured pancreatic cells. However, Spry4 did not significantly affect β–cell tumorigenesis as tumor cells were refractory to Spry4 function. Therefore, cancer cells appear to implement mechanisms that overcome modulation of signal transduction pathways.