Highlights of This Issue

Abstract

Several studies have shown that EGF receptor (EGFR) has a distinct modulatory role in the repair of radiation-induced DNA double-strand breaks, which involves interactions of nuclear EGFR with the DNA repair enzyme, the DNA-dependent protein kinase (DNA-PK). However, the precise mechanism underlying these interactions is not clear. Javvadi and colleagues show that radiation-induced ATM-dependent DNA-PKcs phosphorylation at threonine 2609 is critical for EGFR-DNA-PKcs interaction. The study demonstrates that EGFR binding stabilizes T2609 phosphorylation by preventing DNA-PKcs association with the protein phosphatase, PP2A. These results underscore the EGFR-DNA-PKcs axis as a potential target for tumor radiosensitization.Copper is known to stimulate angiogenesis and thus, potentially, tumor growth. However, prior to this report, the putative role of the metal in cancer cell invasion and metastasis had not been investigated. Parr-Sturgess and colleagues show that copper enhanced the proteolysis of key signaling and adhesion proteins at the cell surface and concomitantly increased the invasion of prostate cancer epithelial cells. Such findings potentially open new avenues for the development of cancer therapies geared towards the prevention of tumor metastasis.Retroelements have been linked to gain of DNA methylation; however, their genome-wide distribution shows enrichment in the vicinity of genes that stay unmethylated in cancer. Estécio and colleagues used transgenes where SINE B1 repeats were inserted upstream to promoters and measured promoter activity, DNA methylation, and histone modifications after transfection in mouse and human cell lines. SINEs interfered negatively with gene expression and promoted epigenetic silencing, whereas CTCF binding sites protected CpG islands from aberrant DNA methylation. These findings confirm that some genes are protected from pressure to become epigenetically silenced while others are vulnerable, and that this difference can be explained by sequence features.The Ah receptor (AHR) has been shown to play an important constitutive role mediating inflammatory signaling in head and neck squamous cell carcinoma (HNSCC) cell lines. In this study, DiNatale and colleagues determined that HNSCC cells have elevated levels of AHR relative to normal keratinocytes, suggesting that targeting the AHR would be selective for tumor cells. AHR antagonism for 24 hours dramatically inhibited the migratory and invasive potential of HN30 cells. Ablating AHR expression also greatly attenuated the migratory potential of HN30 cells. These results suggest that targeting the AHR within the head and neck tumor microenvironment has considerable potential as a nontoxic treatment.