<div>Abstract<p>Although large panels of genes undergoing aberrant CpG island methylation in colorectal cancer have been identified, reliable predictors for clinical management in this tumor type remain elusive. A new DNA methylation signature affecting the extracellular matrix (ECM) pathway has been identified with potential prognostic value in colon cancer. <i>Clin Cancer Res; 17(6); 1215–7. ©2011 AACR</i>.</p></div>
<div>Abstract<p>This report summarizes information presented at the 2015 Keystone Symposium on “MicroRNAs and Noncoding RNAs in Cancer.” Nearly two decades after the discovery of the first miRNA, the role of noncoding RNAs in developmental processes and the mechanisms behind their dysregulation in cancer has been steadily elucidated. Excitingly, miRNAs have begun making their way into the clinic to combat diseases such as hepatitis C and various forms of cancer. Therefore, at this Keystone meeting, novel findings were presented that enhance our view on how small and long noncoding RNAs control developmental timing and oncogenic processes. Recurring themes included (i) how miRNAs can be differentially processed, degraded, and regulated by ribonucleoprotein complexes, (ii) how particular miRNA genetic networks that control developmental process, when disrupted, can result in cancer disease, (iii) the technologies available to therapeutically deliver RNA to combat diseases such as cancer, and (iv) the elucidation of the mechanism of actions for long noncoding RNAs, currently a poorly understood class of noncoding RNA. During the meeting, there was an emphasis on presenting unpublished findings, and the breadth of topics covered reflected how inescapable the influence of noncoding RNAs is in development and cancer. <i>Cancer Res; 75(24); 5206–10. ©2015 AACR</i>.</p></div>
Abstract Cancer is a complex disease in which several molecular and cellular pathways converge to foster the tumoral phenotype. Notably, in the latest iteration of the cancer hallmarks, “nonmutational epigenetic reprogramming” was newly added. However, epigenetics, much like genetics, is a broad scientific area that deserves further attention due to its multiple roles in cancer initiation, progression, and adaptive nature. Herein, we present a detailed examination of the epigenetic hallmarks affected in human cancer, elucidating the pathways and genes involved, and dissecting the disrupted landscapes for DNA methylation, histone modifications, and chromatin architecture that define the disease. Significance: Cancer is a disease characterized by constant evolution, spanning from its initial premalignant stages to the advanced invasive and disseminated stages. It is a pathology that is able to adapt and survive amidst hostile cellular microenvironments and diverse treatments implemented by medical professionals. The more fixed setup of the genetic structure cannot fully provide transformed cells with the tools to survive but the rapid and plastic nature of epigenetic changes is ready for the task. This review summarizes the epigenetic hallmarks that define the ecological success of cancer cells in our bodies.
The Wnt/β-catenin pathway plays critical roles in cell physiology, including determination, proliferation, migration and differentiation in embryonic development and adult homeostasis. Several components of the Wnt/β-catenin pathway, such as SFRPs, WIF-1, DKK-1, APC, AXIN2, ICAT, LEF1 and β-catenin, are the target of mutations or epigenetic inactivation leading to the deregulation or constitutive activation of the Wnt/β-catenin pathway. Aberrant activation of the Wnt signalling pathway abrogates controlled growth and impairs cell differentiation. Alterations of the Wnt signalling pathway have been found in cancer, osteoporosis, ischemic neuronal death and other human diseases. Here we review the alterations of the Wnt/β-catenin signalling cascade and discuss the biological significance and relationship between mutation and/or epigenetic silencing within the same pathway. Keywords: DNA methylation, CpG dinucleotides, Secreted frizzled-related proteins, Dickkopf (Dkk), Adenomatous polyposis coli (APC)
