• Open Access

In This Issue

Tumor-suppressive microRNA-1291 directly regulates glucose transporter 1 in renal cell carcinoma



Yamasaki and colleagues furthered an exciting line of work in which microRNA-1291 (miR-1291) was found to function as a tumor suppressor in renal cell carcinoma-inhibiting cell migration, proliferation, and invasion. In this study, the actual pathways through which miR-1291 functions were investigated. It was discovered, through gene expression analysis, that miR-1291 regulated 79 pathways, the most impressive of which was the direct upregulation of solute carrier family 2 member 1 (SLC2A1). The SLC2A1 gene is responsible for providing instructions for producing glucose transporter protein type 1 (GLUT1), a receptor responsible for the transport of glucose into cells. Not surprisingly, the number of GLUT1 receptors was significantly increased in cancer cells. Moreover, the amount of miR-1291 was significantly inversely correlated with the level of GLUT1 expression. These series of experiments serve to further our understanding of the way a very deadly cancer operates and identifies a potential target for future treatments. doi: 10.1111/cas.12240

Amyloid precursor protein in human breast cancer: An androgen-induced gene associated with cell proliferation


Page 1532–8

In this fascinating study, Takagi et al. explored the role of amyloid precursor protein (APP) in breast cancer. The protein is known to be integral to the pathogenesis of many cancers, as well as Alzheimer's disease. Using human breast tissue and retrospective chart review, it was found that the presence of APP was an independent prognostic factor in samples identified as positive for estrogen receptor. Additionally, it was shown that, in these types of breast cancer, the presence of APP was a significant predictor of recurrence. Interestingly, APP was further discovered to be induced by the androgen dihydrotesterone in both a time- and dose-dependent manner. This study deepens our understanding of the pathophysiology of breast cancer and reveals a potentially important prognostic factor that could be of clinical value to those individuals with estrogen receptor-positive breast cancer. doi: 10.1111/cas.12239

Identification of small molecule inhibitors of p27Kip1 ubiquitination by high-throughput screening


Page 1461–7

Dysregulation of the cell cycle is the foundation upon which all cancers arise. Cyclin-dependent kinases are key factors in cell cycle progression and their activity must be tightly regulated to ensure proper progression and arrest of cellular proliferation. One inhibitor of cyclin-dependent kinases is p27Kip1; when it is degraded, cells may gain the potential to propagate unchecked. One protein important in the degradation of p27Kip1 is Skp2, which is known to possess oncogenic potential. In this exciting study, Ooi and colleagues developed a high-throughput screening system to identify molecular inhibitors of Skp2-mediated p27Kip1 degradation. The authors not only showed the feasibility of their high-throughput technique, but also identified and tested two novel inhibitors of p27Kip1 degradation. This article describes their novel screening method, which may be applied to develop additional potential therapies for a variety of cancers. doi: 10.1111/cas.12246