PDF Version for Printing
Selected Articles from the January 1, 2009 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 January 2009 issue of Molecular Cancer Research
Wang et al.
Page 12
SKP2 has been reported to associate with several kinds of tumors. However, the potential mechanisms are not fully understood. Wang and colleagues observed amplification and overexpression of SKP2 in esophageal squamous cell carcinoma (ESCC), which was correlated with lymph node metastasis. Furthermore, they found for the first time, that SKP2 promoted anoikis resistance through the PI3K-Akt pathway. These findings suggest that SKP2 is an oncogene in the 5p13 amplicon which exerts functions on tumor metastasis in ESCC.
Ayrault et al.
Page 33
Mutations in the Sonic hedgehog (SHH) signaling pathway are found in ~25% of human medulloblasto-mas (MB), which can be modeled in the mouse. Ex-pression of p27Kip1, a cyclin-dependent kinase inhibitor, is restricted to postmitotic neurons in the cerebellum, and its reduced expression in MBs connotes a poor prognosis. Ayrault and colleagues show that mice heterozygous for Ptc1 (the Shh receptor) and that also lack one or two copies of Kip1 frequently develop highly proliferative and invasive MBs. This mouse model closely mimics the vast majority of human MBs that do not sustain TP53 mutations.
Zhang et al.
Page 67
Spontaneous tumors in the dog offer a unique model to study spontaneous tumors in humans. The most commonly mutated gene in human cancers, p53, is found to be altered in dog cancers. Here, Zhang and colleagues established a dog model for the p53 family pathways and showed that dog p53 family proteins have biological activities similar to their human counterparts. Surprisingly, canine p21 cyclin-dependent kinase inhibitor is expressed as two isoforms caused by an unknown modification between residues 129-142. These findings make the dog an excellent out-bred spontaneous tumor model for translational cancer research and a model to study p21 in the cell cycle control.
Solid tumors frequently display areas of severe hypoxia in which HIF is activated. These hypoxic tumors are believed to be more resistant to chemo-therapy and radiation treatment. Knaup and colleagues show that under severe hypoxia, HIF operates independently of mTOR. Therefore, no beneficial effects of mTOR in-hibition may be expected in these regions. Addition-ally, they provide evidence for a novel regulatory interplay of HIF and the rpS6-kinase. Independently of mTOR, HIF is involved in processes governing the phosphorylation status of rpS6, which may influence cellular translational rates and metabolic homeo-stasis. This regulation can also be correlated in an experimental xenograft tumor model.
