The crossroads of adenosinergic pathway and epithelial-mesenchymal plasticity in cancer

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 adeno-sinergic pathway and the EMT program and the impact of this interrelation on cancer development and pro-gression. 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.

Automated summary

Epithelial-mesenchymal transition (EMT) plays a crucial role in tumor progression, invasion, metastasis, therapy resistance, and poor prognosis in various types of cancer. Recent studies have identified a link between the CD73 enzyme and the EMT process. CD73 not only produces the immune suppressant adenosine (ADO), but also acts as a receptor for extracellular matrix proteins, contributing to cell adhesion and migration. The interaction between the adenosinergic pathway and the EMT program significantly impacts cancer development and progression. Analysis of RNAseq datasets reveals a significant correlation between EMT scores and the expressions of NT5E (CD73) and ENTPD1 (CD39) in multiple tumor types, with the strongest correlation observed in prostate adenocarcinoma. The cooperation between EMT and the adenosinergic pathway is context and tumor-dependent. Advancing knowledge in this area will facilitate the exploration of novel treatments and therapies for different types of cancer.