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Abstract
<p class="first" id="d1087761e109">Epithelial-mesenchymal transition (EMT) is a key
mechanism related to tumor progression,
invasion, metastasis, resistance to therapy and poor prognosis in several types of
cancer. However, targeting EMT or partial-EMT, as well as the molecules involved in
this process, has remained a challenge. Recently, the CD73 enzyme, which hydrolyzes
AMP to produce adenosine (ADO), has been linked to the EMT process. This relationship
is not only due to the production of the immunosuppressant ADO but also to its role
as a receptor for extracellular matrix proteins, being involved in cell adhesion and
migration. This article reviews the crosstalk between the adenosinergic pathway and
the EMT program and the impact of this interrelation on cancer development and progression.
An in silico analysis of RNAseq datasets showed that several tumor types have a significant
correlation between an EMT score and NT5E (CD73) and ENTPD1 (CD39) expressions, with
the strongest correlations being in prostate adenocarcinoma. Furthermore, it is evident
that the cooperation between EMT and the adenosinergic pathway in tumor progression
is context and tumor-dependent. The increased knowledge about this topic will help
broaden the view to explore new treatments and therapies for different types of cancer.
</p>
The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics.
The hallmarks of cancer conceptualization is a heuristic tool for distilling the vast complexity of cancer phenotypes and genotypes into a provisional set of underlying principles. As knowledge of cancer mechanisms has progressed, other facets of the disease have emerged as potential refinements. Herein, the prospect is raised that phenotypic plasticity and disrupted differentiation is a discrete hallmark capability, and that nonmutational epigenetic reprogramming and polymorphic microbiomes both constitute distinctive enabling characteristics that facilitate the acquisition of hallmark capabilities. Additionally, senescent cells, of varying origins, may be added to the roster of functionally important cell types in the tumor microenvironment. SIGNIFICANCE: Cancer is daunting in the breadth and scope of its diversity, spanning genetics, cell and tissue biology, pathology, and response to therapy. Ever more powerful experimental and computational tools and technologies are providing an avalanche of "big data" about the myriad manifestations of the diseases that cancer encompasses. The integrative concept embodied in the hallmarks of cancer is helping to distill this complexity into an increasingly logical science, and the provisional new dimensions presented in this perspective may add value to that endeavor, to more fully understand mechanisms of cancer development and malignant progression, and apply that knowledge to cancer medicine.
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