July 1 Cancer Research Highlights

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Selected Articles from the July 1, 2007 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 Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the July 1 issue of Cancer Research.

A Drug Targeting Grb2 Modulates Metastasis

Role of the HPV16 E5 Protein in HPV-Associated Cancers

For years the E5 protein, a potent inducer of growth factor receptors, was considered a key pathogenetic determinant for papillomavirus. But in the mid-1980s, with the discovery of human papillomaviruses (HPV) contributing to cervical cancers, the E6 and E7 proteins assumed more prominent roles. Now E5 is re-emerging in the form of HPV16 E5, expressed in most HPV16-positive cervical cancers. In the current study, Maufort and colleagues use a mouse model to show that HPV16 E5 contributes to two distinct stages of skin carcinogenesis, suggesting that it may play a larger role in HPV-associated human cancers than previously thought. A unique feature of E5-associated carcinogenesis is the endophytic pattern of growth in the benign stage of disease.

Cholesterol Regulates Signal Transduction via Akt

Cholesterol-rich lipid raft microdomains regulate signaling to the serine-threonine kinase Akt. However, direct regulation of Akt by cholesterol has not been shown. Adam and colleagues described a raft-resident subpopulation of endogenous Akt1 with markedly greater cholesterol sensitivity compared with Akt1 elsewhere in cells. Myristoylated Akt1 (MyrAkt1), a potent oncogene, localized preferentially to rafts, exhibited distinct substrate preferences compared with MyrAkt1 in nonraft fractions, and conferred cholesterol-dependent protection from apoptosis. These findings indicate that cholesterol regulates signal transduction by direct effects on Akt and that oncogenic consequences of myristoylation arise, in part, because MyrAkt1 is enriched in cholesterol-rich membranes.

Muscle wasting, the main feature of cachexia, is responsible for the deaths of at least 30% of cancer patients. Implantation of the Yoshida AH-130 ascites hepatoma in rats is a model system for cachectic tumor, which induces a sharp decrease in muscle weight. Fuster and colleagues examined this model to observe whether it induced any changes in gene expression in the peroxisome proliferator-activated receptors (PPARs) and lipid metabolism pathways/proteins in skeletal muscle. Tumor burden increased the expression of PPARδ, PPARγ, PGC1α, and several genes related to fatty acid transport and oxidation; these changes suggested a metabolic shift toward a more oxidative phenotype. Treatment with Formoterol, a β₂-adrenergic agonist, ameliorated the changes caused by the tumor. These results contribute to a better understanding of the role of these transcription factors in skeletalmuscle during cachexia.

Dysregulated Inflammatory Processes Promote Lung Cancer