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View the Table of Contents for the November 15 issue of Cancer Research.
Novak et al. Page 10664
Epigenomic scanning and gene expression profiling were used in this study to define a contiguous region of aberrant methylation and epigenetic silencing encompassing the HOXA gene cluster in human breast cancer. Transcriptional repression occurred within a region of 100 kb in this gene cluster and did not extend to genes located upstream or downstream of the cluster. Novak et al. present evidence that this type of genomic lesion is reversible by a DNA demethylating agent. Together their findings suggest a new type of genomic lesion in cancer that they term an "epigenetic microdeletion," which functionally resembles a genetic deletion, but is defined by epigenetic silencing along a contiguous chromosomal region.
Moskovits et al. Page 10671
Tumor suppressor activities of p53 within cancer cells have been extensively investigated. Moskovits et al. now report that p53 also acts on fibroblasts in tumor stroma by repressing expression and secretion of SDF-1, a chemokine that acts in the CXCR4 pathway to stimulate the migration and invasiveness of tumor cells. Given the well documented contribution of SDF-1 to tumor progression and metastasis, these findings suggest that p53-activating drugs may exert anticancer effects within stromal fibroblasts in tumors as well as on the tumor cells themselves.
Zeng and Berger Page 10701
Mutation of the tumor suppressor gene LKB1, which encodes an evolutionarily conserved serine/threonine kinase, is associated with Peutz-Jeghers syndrome and elevated cancer susceptibility. Previous studies have shown that LKB1 can physically bind to p53 and stabilize it in cells. In this study, Zeng and Berger extend these findings by showing that transcriptional activation of the p53 target gene p21/WAF1, a crucial cell-cycle regulator, is associated with p53-dependent recruitment of LKB1 to the promoter of the p21/WAF1 gene. Notably, genetic fusion of LKB1 to a p53 mutant lacking its activation domain was capable of fully activating transcription of the p21/WAF1 gene. The results indicate that LKB1 has a direct and sufficient role in the ability of p53 to activate this important target gene.
Liu et al. Page 10815
Eph receptors can mediate cell repulsion and migration depending on cell-cell interaction. Members of this class of cell surface receptors are often overexpressed in tumors where they may function in an altered manner. Two articles in this issue of the journal report the possible prognostic value of Eph receptors EphA2 in glioma and EphB4 in ovarian cancers, the overexpression of which are associated with poor clinical outcomes. These findings underscore emerging interest in understanding Eph receptor function in cancer.