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Critical roles of the cAMP-responsive element-binding protein-mediated pathway in disorganized epithelial phenotypes caused by mitochondrial dysfunction


Page 1803–10

Recent evidence suggests that, in addition to mutations in nuclear DNA, mitochondrial DNA aberrancies could contribute to the development of certain types of cancers. Here, Shibanuma and colleagues present their work to further elucidate the biochemical pathway underlying neoplastic transformation of mammary epithelial cells. Using a cell culture model of mitochondrial dysfunction, the authors found that disruptions in cell–cell junctions correlated with the degree of mitochondrial deterioration. Specifically, the presence of E-cadherin was irregular and there was an increased prevalence of actin stress fibers. To better understand the mechanism of this phenomenon, a knockdown of the cAMP-responsive element-binding (CREB) protein was carried out, and recovery in cell–cell junction morphology was observed. Additional experiments were done that indicated that a subcomponent of the CREB pathway, HMGA2, was also involved and that this DNA binding protein is highly expressed in cancer cells taken from humans.doi: 10.1111/j.1349-7006.2012.02369.x

Tax as a molecular target for immunotherapy of adult T-cell leukemia/lymphoma


Page 1764–73

Adult T-cell leukemia/lymphoma (ATL) is a specific type of cancer caused by HTLV-1. Progression of ATL is thought to rely, in part, on the expression of HTLV-1 Tax, a virus-encoded regulatory gene product. Suzuki and colleagues found that expanded Tax-specific CTLs are capable of recognizing and lysing autologous ATL tumor cells in a HLA/Tax epitope peptide complex specific manner. This study helps to clarify the role of Tax in tumor progression and supports the idea that Tax could be a promising molecular target for combating this disease.doi: 10.1111/j.1349-7006.2012.02371.x

Analysis of tumor-induced lymphangiogenesis and lymphatic vessel invasion of pancreatic carcinoma in the peripheral nerve plexus


Page 1756–63

Tumor cells metastasizing through the lymphatic system remains a fairly unexplored domain, despite being the primary pathway by which most tumor cells metastasize. Cheng and coworkers examined 70 ductal adenocarcinoma patients in an attempt to elucidate the role of lymphangiogenesis in the metastasis of pancreatic cancer to the peripheral nerve plexus. Their study suggests that tumor cells are capable of stimulating the growth of lymphocytes in tissue adjacent to the cancer and this is possibly an avenue through which this cancer metastasizes. Moreover, lymphatic vessel density was shown to correlate with peripancreatic nerve plexus invasion, a marker of decreased survival rates. Regulation of lymphangiogenesis through targets such as vascular endothelial growth factor C could be a potential goal for future treatment of adenocarcinomas.doi: 10.1111/j.1349-7006.2012.02364.x